RESUMO
A redução da reatividade vascular à fenilefrina (PE) em aorta de ratas espontaneamente hipertensas (SHR) ao final da prenhez é dependente de maior produção e/ou maior biodisponibilidade de óxido nítrico (NO), consequente do aumento da fosforilação da enzima óxido nítrico sintase endotelial (eNOS) via PI3K/Akt. A glicosilação do tipo N-acetil-glucosamina (O-GlcNAc) é uma modificação pós-traducional que compete com a fosforilação pelos mesmos sítios de ligação nas proteínas. A O-GlcNAcilação da eNOS em serina1177 leva a redução da sua atividade enquanto a fosforilação leva a sua ativação. Além destes mecanismos, a interação da eNOS com outras proteínas é capaz de regular positiva ou negativamente a sua atividade. O objetivo deste trabalho foi analisar possíveis alterações nos mecanismos de modificação pós-traducional que controlam a ativação da eNOS os quais poderiam contribuir para maior ativação e maior biodisponibilidade de NO observada em artérias de ratas prenhes. Foram avaliados o conteúdo proteico O-GlcNAc e também expressão das enzimas que participam desta modificação, O-GlcNAc transferase (OGT) e O-GlcNAcase (OGA) por Western Blotting e a atividade da OGA por ensaio bioquímico em aorta e em artéria mesentérica (2º ou 3º ramo) de ratas não prenhes (NP) e prenhes (P), normotensas (Wistar) e SHR. Ensaios de Western Blotting foram realizados também para análise da expressão das seguintes proteínas: Cav-1, p-Cav-1, CaM e Hsp90. Realizamos a contagem do número de cavéolas endoteliais da aorta e da artéria mesentérica na presença ou ausência da metil-ß-ciclodextrina (dextrina, 10 mmol/L) por microscopia eletrônica. Em estudos funcionais, avaliamos a participação da enzima OGA, pela inibição com PugNAc (100 µmol/L) e das cavéolas, utilizando um desorganizador de cavéolas, a dextrina (10 ou 20 mmol/L), na menor reatividade vascular à PE observada em aortas de ratas P. Observamos que o conteúdo de proteínas O-GlcNAciladas estava diminuído em aorta e em leito mesentérico de ratas Wistar P e SHR P. Apesar da expressão da OGT e da OGA não estar alterada, a atividade da OGA foi aumentada em aorta e leito mesentérico de ratas Wistar P, mas, encontra-se diminuída em aorta e aumentada em leito mesentérico de SHP P. A incubação com PugNAc reverteu a reduzida reatividade à PE em aorta e artéria mesentérica de ratas Wistar P mas este efeito não foi observado em vasos SHR P, demonstrando que a OGA parece ter um papel importante na redução da O-GlcNAcilação de proteínas vasculares em Wistar P. Em vasos incubados com PugNAc, a remoção do endotélio ou a incubação com L-NAME, não alterou significativamente a reatividade à PE. Juntos estes resultados sugerem que a maior atividade da eNOS observada em vasos de Wistar P, fica prejudicada na presença do PugNAc, e depende da atividade da OGA. Como não houve alteração da resposta contrátil à PE em vasos de SHR P incubados com PugNAc, possivelmente um mecanismo diferente, envolvendo a menor atividade da OGT, ocorre nestas artérias para a redução da O-GlcNAcilação da eNOS. A desorganização das cavéolas por meio da dextrina causou aumento de contração à PE e redução de potência da ACh em aortas de Wistar NP e SHR NP, porém não houve alteração em aortas de ratas Wistar P e SHR P. A dextrina não alterou o número de cavéolas em artérias de Wistar P e SHR P quando comparado com ratas NP. SHR NP apresentam um reduzido número de cavéolas das aortas em relação a Wistar NP bem como expressão reduzida de Cav-1, p-Cav-1 e CaM. A prenhez não foi capaz de alterar a expressão da Cav-1, CaM e Hsp90 em aorta e leito mesentérico de ratas normotensas e hipertensas. Estes resultados sugerem que a prenhez não altera a expressão das proteínas Cav-1, CaM e Hsp90 e possivelmente a interação com a eNOS em aorta e artérias mesentéricas de ratas normotensas e hipertensas. Em conclusão, entre os mecanismos estudados de modificação pós-traducional da eNOS, a redução da O-GlcNAcilação da eNOS, por mecanismos que envolvem a atividade da OGA e possivelmente da OGT, favoreceria a fosforilação da eNOS e consequente maior biodisponibilidade de NO, contribuindo desta forma para modulação da resposta contrátil da PE nas artérias de ratas P(AU)
Reduction of vascular reactivity to phenylephrine (PE) in aorta of spontaneously hypertensive rats (SHR) at the end of pregnancy is dependent on higher production and/or higer bioavailability of nitric oxide (NO), as a consequence of increased endothelial nitric oxide synthase enzyme (eNOS) phosphorylation, by PI3K/Akt. Glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification that competes with phosphorylation by the same binding sites in proteins. O-GlcNAcylation of eNOS on serine site leads to a reduction in its activity while eNOS phosphorylation leads to its activation. In addition to these mechanisms, the interaction of eNOS with other proteins is able to regulate positively or negatively its activity. The objective of this study was to analyze possible changes in the mechanisms of post-translational modification that control the eNOS activation, which could contribute to its the greater activation and greater bioavailability of NO observed in arteries of pregnant rats. The O-GlcNAc-protein content and also the enzymes expression that participate in this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) was assessed by Western Blotting, and OGA activity were evaluated by biochemical assay in the aorta and in the artery mesenteric (2nd or 3rd branch) of non-pregnant (NP) and pregnant (P), normotensive rats (Wistar) and SHR. Western Blotting assays were also performed for expression analysis of the following proteins: Cav-1, p-Cav-1, CaM and Hsp90. We performed the counting of the number of endothelial caveolae in the aorta and the mesenteric artery in the presence or absence of methyl-ß-cyclodextrin (dextrin, 10 mmol/L) by electronic microscopy. In functional studies, we evaluated the participation of the OGA enzyme, by inhibition with PugNAc (100 µmol/L) and of the caveolae, using a caveolae disassembler, dextrin (10 or 20 mmol/L), in the reduced vascular reactivity observed in aortas or mesenteric arteries of P rats. We observed that the content of O-GlcNAcylated proteins was decreased in the aorta and in the mesenteric bed of Wistar P and SHR P rats. Although OGT and OGA expression is not altered, OGA activity was increased in the aorta and mesenteric bed of Wistar P rats but was decreased in the aorta and increased in the mesenteric bed of SHP P. Incubation with PugNAc reversed the reduced reactivity to PE in the aorta and mesenteric artery of Wistar P but this effect was not observed in SHR P arteries, demonstrating that OGA appears to play an important role in reducing O-GlcNAcylation of vascular proteins in Wistar P. In arteries incubated with PugNAc, endothelial removal or incubation with L-NAME did not significantly alter reactivity to PE. Together, these results suggest that the greater eNOS activity observed in Wistar P vessels was impaired in the presence of PugNAc, and it depends on OGA activity. As there was no change in the contractile response to PE in SHR P arteries incubated with PugNAc, possibly a different mechanism, involving the lower activity of OGT, occurs in these vessels for the reduction of O-GlcNAcylation of eNOS. Dextrin caused increased contraction of PE and decreased ACh potency in Wistar NP and SHR NP aortas, but there was no change in aortas of Wistar P and SHR P. Dextrin did not alter the number of cavelae in Wistar P and SHR P arteries compared to NP rats. SHR NP showed a lower number of caveolae than to NP Wistar as well reduced expression of Cav-1 and CaM. Pregnancy was not able to alter the expression of Cav-1, CaM and Hsp90 in the aorta and mesenteric bed of normotensive and hypertensive rats. These results suggest that pregnancy does not alter the expression of Cav-1, CaM and Hsp90 proteins and possibly interaction with eNOS in the aorta and mesenteric arteries of normotensive and hypertensive rats. In conclusion, among the studied mechanisms of post-translational modification of eNOS, the reduction of O-GlcNAcylation of eNOS, by mechanisms that involve OGA activity and possibly OGT, would favor eNOS phosphorylation and consequent greater NO bioavailability, contributing in this way for modulation of the contractile response to PE in the arteries of P rats(AU)
Assuntos
Animais , Feminino , Gravidez , Aorta , Óxido Nítrico Sintase , Hipertensão , Glicosilação , Calmodulina , Ratos Wistar , Proteínas de Choque Térmico HSP90 , Caveolina 1 , Artérias MesentéricasRESUMO
Objective To observe the mRNA and protein expression of thyroglobulin (Tg) and thyroid peroxidase (TPO) in each trimester of pregnant and lactating Wistar rats.Methods Ninety-six SPFNAF Wistar rats (84 female and 12 male),weighting 220-260 g were involved.All female Wistar rats were randomly divided into 7 groups according to their body mass via the random number table method:control group,early pregnancy group (7 d),midpregnancy group (14 d),late pregnancy group (21 d),early lactation group (7 d),midlactation group (14 d) and late lactation group (21 d),12 rats in each group.The rats were fed with conventional feed and drank deionized water freely.Female rats of the last 6 groups were mated with male rats.Thyroids were collected on the 7 d,14 d and 21 d of their pregnancy and lactation,respectively.The mRNA expression levels of Tg and TPO were detected by quantitative real-time PCR,and the protein expression levels of Tg and TPO were detected by Western blotting.Results The expression levels of Tg mRNA in thyroid tissue in the control group,early,middle and late pregnancy and early,middle and late lactation (1.05 ± 0.01,3.20 ± 0.23,1.88 ± 0.12,2.69 ± 0.20,1.53 ± 0.19,2.37 ± 0.31,2.23 ± 0.12) were significantly different between groups (F =42.864,P ＜ 0.05),and those of pregnancy and lactation groups were higher than those in the control group (P ＜ 0.05).The expression levels of Tg protein were 0.15 ± 0.01,0.38 ± 0.01,0.32 ± 0.02,0.37 ± 0.01,0.21 ± 0.01,0.35 ± 0.01,0.44 ± 0.01,respectively.The differences between groups were statistically significant (F =232.250,P ＜ 0.05).And those of pregnancy and lactation groups were higher than those in the control group (P ＜ 0.05).The expression levels of TPO mRNA in thyroid tissue in the control group,early,middle and late pregnancy and early,middle and late lactation (0.57 ± 0.01,0.74 ± 0.03,0.78 ± 0.13,1.08 ± 0.10,0.98 ± 0.10,1.00 ± 0.07,0.76 ± 0.05) were significantly different between groups (F =15.448,P ＜ 0.05).And those of pregnancy and lactation groups were higher than those in the control group (P ＜ 0.05).The expression of TPO protein were 0.23 ± 0.01,0.41 ± 0.01,0.72 ± 0.02,0.78 ± 0.01,0.49 ± 0.01,0.52 ± 0.01,0.45 ± 0.02,respectively.The differences between groups were statistically significant (F =563.692,P ＜ 0.05).And those of pregnancy and lactation groups were higher than those in the control group (P ＜ 0.05).Conclusions The mRNA and protein expression levels of TPO and Tg have increased in pregnant and lactating rats.This performance may be raleted to thyroid hormone deficiency and mild hypothyroidism.
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Objective: The effects of prenatal exposure to brominated diphenyl ethers-209 to the Influence of male offspring rats hippocampus BDNF potein expression and its mechanism of action. Methods: Pregnant Sprague-Dawley (SD) rats were randomly treated with BDE-209 (100, 300, and 900 mg/kg body weight) or corn oil by gavage on gestational days 6-20. Blood was obtained through heart puncture for thyroid hormone analysis in male rats offspring on PND 60. The hippocampus tissues were excised. The expression levels of BDNF protein were measured by Western blot. Results: 1) In hippocampal tissue, BDNF protein expression concentration ratio relative to the control group (control group concentration of 1) were 0.87 (300 mg/kg dose group) and 0.67 (900 mg/kg) (P<0.01) . 2) Compared to controls, total T4 levels and free T4 levels were significantly decreased in the BDE-209 treated-group (900 mg/kg, 300 mg/kg) (P<0.05) . Total T3 levels in 300 mg/kg group were also significantly decreased compared to the control (P<0.05) . However, no significant difference was observed in 100 mg/kg group (P>0.05) . Conclusion: During 300 and 900 mg/kg dose group of BDE-209 exposure to male offspring BDNF protein expression in rat hippocampus decreased, may be related to its interference with thyroid hormone.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Éteres Difenil Halogenados/toxicidade , Hipocampo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Troca Materno-Fetal , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Objective@#The effects of prenatal exposure to brominated diphenyl ethers-209 to the Influence of male offspring rats hippocampus BDNF potein expression and its mechanism of action.@*Methods@#Pregnant Sprague-Dawley (SD) rats were randomly treated with BDE-209 (100, 300, and 900 mg/kg body weight) or corn oil by gavage on gestational days 6-20. Blood was obtained through heart puncture for thyroid hormone analysis in male rats offspring on PND 60. The hippocampus tissues were excised. The expression levels of BDNF protein were measured by Western blot.@*Results@#1) In hippocampal tissue, BDNF protein expression concentration ratio relative to the control group (control group concentration of 1) were 0.87 (300 mg/kg dose group) and 0.67 (900 mg/kg) (P<0.01) . 2) Compared to controls, total T4 levels and free T4 levels were significantly decreased in the BDE-209 treated-group (900 mg/kg, 300 mg/kg) (P<0.05) . Total T3 levels in 300 mg/kg group were also significantly decreased compared to the control (P<0.05) . However, no significant difference was observed in 100 mg/kg group (P>0.05) .@*Conclusion@#During 300 and 900 mg/kg dose group of BDE-209 exposure to male offspring BDNF protein expression in rat hippocampus decreased, may be related to its interference with thyroid hormone.
RESUMO
Estudos têm mostrado que em ratas prenhas normotensas ou hipertensas (SHR) há uma diminuição significativa da pressão arterial nos períodos finais da prenhez diretamente associada à redução da atividade simpática perivascular de leitos mesentéricos de ratas normotensas ou hipertensas (SHR). Essas alterações têm sido atribuídas a uma importante participação dos fatores relaxantes derivados do endotélio com destaque ao óxido nítrico (NO). Estudos recentes do nosso laboratório sugerem que o aumento da síntese de NO pela enzima óxido nítrico sintase endotelial (eNOS) ao final da prenhez ocorre por uma via menos dependente de cálcio, associada a fosforilação da eNOS em resíduos de Serina 1177, através da via PI3K/Akt/eNOS. Por outro lado, ratas hipertensas não prenhas apresentam uma disfunção endotelial e vascular ocasionada pelo aumento na produção de espécies reativas de oxigênio (ERO), sendo o complexo enzimático NAD(P)H oxidase, uma importante fonte de ERO. A produção de ERO modula a biodisponibilidade de NO. Assim, uma diminuição das ERO durante a prenhez poderia contribuir para a redução da PA e modulação da reatividade vascular, dependente do endotélio, aos agonistas vasoconstritores. Nossa hipótese é que em SHR prenhas, a redução da produção de ERO na aorta contribuiria para o aumento da biodisponibilidade do NO e para a hiporreatividade de aortas à fenilefrina (PE). Para isso, o estresse oxidativo sistêmico e da aorta (TBARS) foram avaliados em ratas Wistar e SHR, prenhas (P) e não prenhas (NP). Analisamos o efeito hipotensor da Apocinina (30 mg/kg) e do Tempol (30 mg/kg). Anéis intactos de aorta torácica de P e NP foram estimulados com PE antes e após incubação (30 min) com Apocinina (100 μmol/L) ou Tempol (0,1 nmol/L). O efeito de Apocinina e do Tempol foi avaliado nas concentrações citosólicas de NO ([NO]), medidas pela intensidade de fluorescência do DAF-2DA (10 µmol/L), de ERO ([ERO]), medida pelo DHE (2,5 µmol/L) e Ca2+, medida pelo FLUO 3-AM...
Studies have shown that in normotensive or hypertensive pregnant rats (SHR) there is a significant decrease in blood pressure in late pregnancy directly associated with the reduction in sympathetic perivascular activity of mesenteric beds of normotensive or hypertensive rats (SHR). These changes have been attributed to an important role of endothelium-derived relaxing factors especially to nitric oxide (NO). Recent studies in our laboratory suggest that increased synthesis of NO by endothelial nitric oxide synthase (eNOS) in late pregnancy is of a less calcium-dependent pathway associated with phosphorylation of eNOS on serine 1177 through via PI3K/Akt/ eNOS. On the other hand, do not exhibit a pregnant hypertensive rats and the vascular endothelial dysfunction caused by increased production of reactive oxygen species (ROS), the NAD(P)H oxidase enzyme complex, a major source of ROS. The ROS modulate the bioavailability of NO. Thus, a reduction of ROS during pregnancy could contribute to the reduction in blood pressure and modulation of vascular reactivity endothelium-dependent, to vasoconstrictor agonists. Our hypothesis is that in pregnant spontaneous hypertensive rats (SHR), the reduction of ROS production in the aorta contribute to increase the bioavailability of NO and hyporeactivity to aortae phenylephrine (PE). For this reason, systemic oxidative stress and aorta (TBARS) were valued in Wistar and SHR rats, pregnant (P) and non-pregnant (NP). We analyzed the hypotensive effect of Apocynin (30 mg/kg) and Tempol (30 mg/kg). Intact rings of thoracic aorta of P and NP were stimulated with PE before and after incubation (30 min) with apocynin (100 mmol/L) or Tempol (0,1 nmol/L). The effect of Apocynin and Tempol was evaluated in the cytosolic concentration of NO ([NO]) as measured by fluorescence intensity of DAF-2DA (10 µmol/L), ROS ([ROS]), as measured by DHE (2,5 µmol/L) and Ca2+, as measured by FLUO-3 AM (5 µmol/L) in isolated aortic endothelial cells. We...
Assuntos
Animais , Ratos , Aorta , Endotélio , Espécies Reativas de Oxigênio , Hipertensão , Prenhez , Ratos Endogâmicos SHR , Ratos WistarRESUMO
Estudos têm mostrado que em ratas prenhas normotensas ou hipertensas (SHR) há uma diminuição significativa da pressão arterial nos períodos finais da prenhez diretamente associada à redução da atividade simpática perivascular de leitos mesentéricos de ratas normotensas ou hipertensas (SHR). Essas alterações têm sido atribuídas a uma importante participação dos fatores relaxantes derivados do endotélio com destaque ao óxido nítrico (NO). Estudos recentes do nosso laboratório sugerem que o aumento da síntese de NO pela enzima óxido nítrico sintase endotelial (eNOS) ao final da prenhez ocorre por uma via menos dependente de cálcio, associada a fosforilação da eNOS em resíduos de Serina 1177, através da via PI3K/Akt/eNOS. Por outro lado, ratas hipertensas não prenhas apresentam uma disfunção endotelial e vascular ocasionada pelo aumento na produção de espécies reativas de oxigênio (ERO), sendo o complexo enzimático NAD(P)H oxidase, uma importante fonte de ERO. A produção de ERO modula a biodisponibilidade de NO. Assim, uma diminuição das ERO durante a prenhez poderia contribuir para a redução da PA e modulação da reatividade vascular, dependente do endotélio, aos agonistas vasoconstritores. Nossa hipótese é que em SHR prenhas, a redução da produção de ERO na aorta contribuiria para o aumento da biodisponibilidade do NO e para a hiporreatividade de aortas à fenilefrina (PE). Para isso, o estresse oxidativo sistêmico e da aorta (TBARS) foram avaliados em ratas Wistar e SHR, prenhas (P) e não prenhas (NP). Analisamos o efeito hipotensor da Apocinina (30 mg/kg) e do Tempol (30 mg/kg). Anéis intactos de aorta torácica de P e NP foram estimulados com PE antes e após incubação (30 min) com Apocinina (100 μmol/L) ou Tempol (0,1 nmol/L). O efeito de Apocinina e do Tempol foi avaliado nas concentrações citosólicas de NO ([NO]), medidas pela intensidade de fluorescência do DAF-2DA (10 µmol/L), de ERO ([ERO]), medida pelo DHE (2,5 µmol/L) e Ca2+, medida pelo FLUO 3-AM...
Studies have shown that in normotensive or hypertensive pregnant rats (SHR) there is a significant decrease in blood pressure in late pregnancy directly associated with the reduction in sympathetic perivascular activity of mesenteric beds of normotensive or hypertensive rats (SHR). These changes have been attributed to an important role of endothelium-derived relaxing factors especially to nitric oxide (NO). Recent studies in our laboratory suggest that increased synthesis of NO by endothelial nitric oxide synthase (eNOS) in late pregnancy is of a less calcium-dependent pathway associated with phosphorylation of eNOS on serine 1177 through via PI3K/Akt/ eNOS. On the other hand, do not exhibit a pregnant hypertensive rats and the vascular endothelial dysfunction caused by increased production of reactive oxygen species (ROS), the NAD(P)H oxidase enzyme complex, a major source of ROS. The ROS modulate the bioavailability of NO. Thus, a reduction of ROS during pregnancy could contribute to the reduction in blood pressure and modulation of vascular reactivity endothelium-dependent, to vasoconstrictor agonists. Our hypothesis is that in pregnant spontaneous hypertensive rats (SHR), the reduction of ROS production in the aorta contribute to increase the bioavailability of NO and hyporeactivity to aortae phenylephrine (PE). For this reason, systemic oxidative stress and aorta (TBARS) were valued in Wistar and SHR rats, pregnant (P) and non-pregnant (NP). We analyzed the hypotensive effect of Apocynin (30 mg/kg) and Tempol (30 mg/kg). Intact rings of thoracic aorta of P and NP were stimulated with PE before and after incubation (30 min) with apocynin (100 mmol/L) or Tempol (0,1 nmol/L). The effect of Apocynin and Tempol was evaluated in the cytosolic concentration of NO ([NO]) as measured by fluorescence intensity of DAF-2DA (10 µmol/L), ROS ([ROS]), as measured by DHE (2,5 µmol/L) and Ca2+, as measured by FLUO-3 AM (5 µmol/L) in isolated aortic endothelial cells. We...
Assuntos
Animais , Ratos , Aorta , Endotélio , Espécies Reativas de Oxigênio , Hipertensão , Prenhez , Ratos Endogâmicos SHR , Ratos WistarRESUMO
Objective To evaluate the effect of maternal diabetes on the blood pressure and kidney function of female offspring, as well as if such changes exacerbate during pregnancy. Methods Diabetes mellitus was induced in female rats with the administration of streptozotocin in a single dose, one week before mating. During pregnancy, blood pressure was measured through plethysmography. On the 20th day of pregnancy, the animals were placed for 24 hours in metabolic cages to obtain urine samples. After the animals were removed from the cages, blood samples were withdrawn. One month after pregnancy, new blood and urine sample were collected. Kidney function was evaluated through proteinuria, plasma urea, plasma creatinine, creatinine excretion rate, urinary flow, and creatinine clearance. Results The female offspring from diabetic mothers showed an increase in blood pressure, and a decrease in glomerular filtration rate in relation to the control group. Conclusion Hyperglycemia during pregnancy was capable of causing an increase in blood pressure and kidney dysfunction in the female offspring. .
Objetivo Avaliar o efeito do diabetes materno sobre a pressão arterial e a função renal da prole feminina, bem como verificar se as alterações observadas se exacerbam durante a prenhez. Métodos O diabetes mellitus foi induzido em ratas com a administração de estreptozocina em dose única, uma semana antes do cruzamento. Durante a prenhez, foram feitas medidas da pressão arterial por pletismografia. No 20o dia da prenhez, os animais foram colocados durante 24 horas em gaiolas metabólicas para obtenção de amostras de urina. Após a retirada dos animais das gaiolas, foram obtidas amostras de sangue. Um mês após a prenhez, foram obtidas novas amostras de sangue e urina para as determinações. A função renal foi avaliada por meio de proteinúria, ureia plasmática, creatinina plasmática, carga excretada de creatinina, fluxo urinário e clearance de creatinina. Resultados As fêmeas da prole de mães diabéticas apresentaram elevação da pressão arterial e redução do ritmo de filtração glomerular em relação ao grupo controle. Conclusão A hiperglicemia durante a gestação foi capaz de causar elevação da pressão arterial e disfunção renal na prole de sexo feminino. .
Assuntos
Animais , Feminino , Gravidez , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/etiologia , Hipertensão/etiologia , Gravidez em Diabéticas , Efeitos Tardios da Exposição Pré-Natal/etiologia , Creatinina/sangue , Modelos Animais de Doenças , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/fisiopatologia , Idade Gestacional , Taxa de Filtração Glomerular , Hiperglicemia/complicações , Hipertensão/fisiopatologia , Rim/fisiopatologia , Gravidez em Diabéticas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Proteinúria/urina , Ratos Wistar , Valores de Referência , Estreptozocina , Fatores de Tempo , Ureia/sangueRESUMO
Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the N-methyl-D-aspartate (NMDA) receptor expression in offspring rat hippocampus.Methods Thirty female adult Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly assigned into 5 groups (n =6 each):control group (group C),exposure to isoflurane before gestation group (group BI),exposure to isoflurane during gestation period group (group PI),exposure to sevoflurane before gestation group (group BS),exposure to sevoflurane during gestation period group (group PS).The rats inhaled 1.6％ isoflurane for 6 h at 1 day before gestation in group BI.The rats inhaled 1.6％ isoflurane for 6 h at 6,10,14 and 18 day gestation in group PI.The rats were exposed to 2.4％ sevoflurane for 6 h before gestation in group BS.The rats were exposed to 2.4％ sevoflurane for 6 h at 6,10,14 and 18 day gestation in group PS.Twelve offspring rats from pregnant rats in each group were chosen on the day of birth (T1),and 7th,14th and 28th days after birth (T2-4) and sacrificed,and the hippocampi were then isolated for determination of the expression NMDA receptor (NR1,NR2A and NR2B).Results Compared with group C,no significant change was found in NMDA receptor expression in off spring rat hippocampus in groups BI and BS (P ＞ 0.05),and the expression of NR1 and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1-3 (P ＜0.05),and no significant change was found in NMDA receptor expression at T4 in groups PI and PS (P ＞ 0.05).Compared with group PI,the expression of NRI and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1 3 (P ＜ 0.05 or 0.01),and no significant change was found in N MDA receptor expression at T4 in group PS (P ＞ 0.05).Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the NMDA receptor expression in offspring rat hippocampus,while isoflurane or sevoflurane inhalation after gestation can induce abnormal expression of the NMDA receptor in offspring rat hippocampus,which may result in apoptosis in hippocampal cells and abnormality in the development of nervous system and cognitive function.
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PURPOSE: To evaluate hepatic morphological-histological abnormalities in newborns from female rats exposed to ethylenethiourea. METHODS: A randomized study was conducted on fifty-five newborn Wistar rats were studied: 34 in the experimental group, whose mothers had been exposed to 1% ethylenethiourea; and 21 in the control group, whose mothers had received 0.9% physiological solution. The solution was administered via gavage on the 11th day of gestation. Cesarean section was performed on the 20th day of gestation. The newborns' livers were examined and any morphological-histological abnormalities were registered. The presence of megakaryocytes was quantified in 50 microscope fields, as the total number of these cells per mm². RESULTS: The entire experimental group presented abnormalities of embryonic formation, with musculoskeletal anomalies, digestive system anomalies, hepatic congestion and friability, hydrops and delayed intrauterine growth. The histopathological analysis showed that morphological-histological hepatic destructuring had occurred in all entire experimental with removal of the hepatic trabeculae and severe hepatic megakaryocytosis. The mean megakaryocyte density ranged from 107.9 to 114.2 per mm², and it was eight times greater than in the control group, thus characterizing a situation of extramedullary hematopoiesis. CONCLUSION: The fetal exposure to ethylenethiourea caused hepatic damage characterized by severe extramedullary hematopoiesis.
OBJETIVO: Avaliar alterações hepáticas morfohistológicas em recém-nascidos de ratas prenhes expostas à etilenotioureia. MÉTODOS: Realizado ensaio randomizado em animais de experimentação, onde foram estudados 55 recém-nascidos de ratas Wistar, 34 do Grupo Experimento, expostas a etilenotioureia 1% e 21 do Grupo Controle, em que a rata prenhe recebeu solução fisiológica 0,9%, ambos por gavagem no 11º dia de gestação. Realizada no 20º dia de gestação cesariana, analisados os fígados dos recém-nascidos e registradas as alterações morfohistológicas. Realizou-se a quantificação dos megacariócitos em 50 campos microscópicos, avaliando a quantidade total destas células por mm². RESULTADOS: Todos os recém-nascidos do Grupo Experimento apresentaram alterações na formação embrionária, com anomalias musculoesqueléticas, anormalidades do sistema digestório, congestão e friabilidade hepática, hidropisia e crescimento intrauterino retardado. A análise histopatológica mostrou desestruturação hepática morfohistológica em todos os recém-nascidos expostos à etilenotioureia, com destrabeculação dos hepatócitos e intensa megacariocitose hepática, apresentando média da densidade de megacariócitos de 107,9 até 114,2 por mm² sendo cerca de oito vezes maior que no Grupo Controle, caracterizando hematopoese extramedular. CONCLUSÃO: A exposição fetal a etilenotioureia provocou danos hepáticos caracterizados pela intensa hematopoese extramedular.
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Animais , Feminino , Gravidez , Ratos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Etilenotioureia/toxicidade , Praguicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais Recém-Nascidos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hematopoese Extramedular/efeitos dos fármacos , Modelos Animais , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Distribuição Aleatória , Ratos WistarRESUMO
Objective To investigate the effect of di-( 2-ethylhexyl ) phthalate (DEHP) on pregnant rat and the protection of zinc.Methods Fifty rats were randomized equally into 5 groups consisting of blank (given 1 ml 0.9％ sodium chloride),corn oil (given 1 ml corn oil),zinc (given 1 ml zinc gluconate including 1.2 mg zinc),DEHP (given 50 mg · kg-1 · d-1 DEHP)and DEHP + zinc (given 50 mg· kg-1 · d-1 DEHP + zinc gluconate ).At the beginning of the experiment (about 7 d before pregnancy),the female rats were administered with corresponding drugs everyday.The pregnant rats were killed and the fetal rats were removed on 19th day.The following results in each group were recorded:the body weight and the organic weight of the female rats,the number and the weight of fetus rats and the placental weight.Results The weight and the coefficient of female rats' kidney/body,spleen/body,brain/ body,and heart/body in DEHP group compared with other groups were not statistical significance (all P ＞0.05).The coefficient of female rats' liver/body,uterus/body,and ovary/body of blank group were (4.4 ± 0.7 ) ％,( 1.26 ± 0.09 ) ％,( 0.083 ± 0.009 ) ％ respectively,corn oil group were (4.5 ± 0.6 ) ％,( 1.29 ±0.10)％,(0.084 ±0.008)％,zinc group were (4.4 ±0.4)％,( 1.26 ±0.08)％,(0.084 ± 0.009 ) ％,DEHP group were ( 5.4 ± 1.0 ) ％,( 1.11 ± 0.08 ) ％,( 0.074 ± 0.012 ) ％,and DEHP + zinc group were (4.4 ± 1.0)％,( 1.28 ± 0.10)％,(0.082 ± 0.007)％ ; in DEHP group the coefficient of female rats' liver/body,uterus/body,and ovary/body compared with other groups was statistical significance ( P ＜ 0.05 ).The fetal quantity,fetal weight and placental weight of female rats of blank group were 12.8 ± 2.7,(6.03 ±0.16) g,( 1.00 ±0.03) g respectively,corn oil group were 13.6 ±3.1,(6.07 ±0.20) g,(1.00±0.04) g,zinc group were 13.3 ±3.1,(6.16 ±0.18) g,( 1.00 ±0.05) g,DEHP group were 9.2±4.1,(4.03 ±0.09) g,(0.95 ±0.03) g,and zinc +DEHP group were 12.1 ±2.9,(6.09 ± 0.17 ) g,(0.99 ±0.03 ) g.In DEHP group the fetal quantity,fetal weight and placental weight of female rats compared with other groups were statistical significance ( P ＜ 0.05 ).Conclusion DEHP can damage female rats and fetal rats in gestation period.Zinc supplied before pregnancy can relieve the influence by DEHP.
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OBJETIVO: avaliar os efeitos da administração da associação zidovudina-lamivudina-ritonavir nos fígados e rins de ratas prenhes e seus conceptos do ponto de vista morfológico e fisiológico. MÉTODOS: 40 ratas albinas prenhes foram aleatoriamente divididas em 4 grupos: 1 controle (Ctrl: controle de veículo) e 3 experimentais (Exp1x, Exp3x e Exp9x). Estes últimos foram tratados por solução oral de zidovudina/lamivudina/ritonavir (Exp1x: 10/5/20 mg/kg; Exp3x: 30/15/60 mg/kg; Exp9x: 90/45/180 mg/kg). As drogas e o veículo foram administrados por gavagem, desde o 1º até o 20º dia de prenhez. No último dia do experimento, todos os animais foram anestesiados e sangue foi retirado da cavidade cardíaca para avaliação sérica das enzimas aspartato aminotransferase (AST) e alanina aminotransferase (ALT), por método calorimétrico, bem como da ureia, determinada por método cinético-enzimático, e creatinina, por método cinético-colorimétrico. Em seguida, fragmentos dos fígados e rins maternos e fetais foram coletados, fixados em formol a 10 por cento e processados segundo os métodos histológicos para inclusão em parafina. Cortes com 5 µm de espessura foram corados pela hematoxilina-eosina (HE) e analisados por microscopia de luz. Na leitura das lâminas, considerou-se o padrão de normalidade para fígado e rins, tais como: hepatócitos, espaço porta íntegros e veias hepáticas bem definidas. Nos rins, a presença de corpúsculos renais, túbulos contorcidos e alças de Henle típicos. Nos fígados fetais considerou-se, ainda, a morfologia das células da linhagem eritrocitária nas diferentes fases do desenvolvimento, bem como os megacariócitos. Quando houve alteração da coloração padrão estabelecida para as estruturas hepáticas e renais, alteração na morfologia de núcleos, rompimento de limites de alguma organela citoplasmática, presença de congestão vascular, tudo isso foi entendido como provavelmente provocado pelas drogas em sua(s) dose(s) de aplicação. A avaliação estatística foi realizada por análise de variância (ANOVA), completada pelo teste de Tukey-Kramer (p<0,05). RESULTADOS: os fígados maternos dos grupos Ctrl, Exp1x e Exp3x mostraram hepatócitos típicos, espaço porta íntegros e veias hepáticas com aspecto normal. No fígado materno do grupo Exp9x, foram encontrados hepatócitos com sinais de atrofia e apoptose (eosinofilia citoplasmática e núcleos picnóticos). Além disso, identificou-se vasodilatação dos capilares sinusoides (congestão). Os rins maternos dos grupos Ctrl e Exp1x apresentaram-se normais, com corpúsculos renais, túbulos contorcidos e alças de Henle típicos. Já nos grupos Exp3x e Exp9x, foram encontrados congestão vascular, glomérulos pequenos ricos em células contendo núcleos hipercromáticos, sendo mais intensos no Exp9x. Com relação aos fígados e rins fetais, não foram observadas alterações morfológicas ou fisiológicas nos grupos estudados. Encontrou-se aumento significante nos níveis da AST (305,70±55,80; p<0,05) e da creatinina (0,50±0,09; p<0,05) no grupo Exp9x. CONCLUSÕES: nossos resultados evidenciam que a administração da associação zidovudina/lamivudina/ritonavir a ratas prenhes em altas doses causa alterações morfológicas e funcionais nos fígados e rins maternos. Não houve alterações nem morfológicas nem fisiológicas nos fígados e rins fetais.
PURPOSE: to evaluate the effect of administration of three different doses of the zidovudine/lamivudine/ritonavir combination on the liver and kidneys of pregnant rats and their concepts from a morphological and physiological standpoint. METHODS: 40 pregnant EPM-1 Wistar rats were randomly divided into 4 groups: 1 control (Ctrl: drug vehicle control, n=10) and 3 experimental groups: Exp1x, Exp3x and Exp9x. An oral solution of the zidovudine/lamivudine/ritonavir combination was administered to the experimental groups from the day 0 to day 20 of pregnancy: Exp1x=10/5/20 mg/kg; Exp3x=30/15/60 mg/kg; Exp9x=90/45/180 mg/kg. On the 20th pregnancy day the rats were anesthetized and blood was taken directly from the ventricular chambers for further biochemical determinations: aspartate-(AST) and alanine-(ALT) aminotransferases (Calorimetric method), urea nitrogen (BUN) by an enzymatic-kinetic method, and creatinine by a kinetic-calorimetric method. Maternal and fetal liver and kidney samples were taken, fixed in 10 percent formaldehyde and processed histologically for paraffin embedding. Five µm-thick fragments of maternal and fetal livers and kidneys were stained with hematoxilyn-eosin, being analyzed by light microscopy. To interpret the results, the well-known pattern of normality for livers and kidneys was considered on the basis of the following structures: hepatocytes, portal structure, hepatic veins, renal corpuscles, renal tubules and loop of Henle. Regarding the fetal livers, we also considered the erythrocytes in their different stages of development as well as the megacariocytes. If there was a change in the established staining pattern for liver and kidney structures, changes in nuclear morphology, rupture of some cytoplasmic organelles, and presence of vascular congestion, this was considered to be due to the drug doses. Results were submitted to analysis of variance (ANOVA) and to the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: no morphological changes were observed in the maternal livers of the Ctrl, Exp1x and Exp3x groups. In the maternal liver of the Exp9x group, hepatocytes showed signs of atrophy and apoptosis (eosinophilic cytoplasm and pycnotic nuclei) and marked sinusoid capillary vasodilation (congestion) was observed. The maternal kidneys of the Ctrl and Exp1x groups were normal, with renal corpuscles, convoluted tubules and typical loops of Henle. In contrast, the Exp3x and Exp9x groups showed vascular congestion and small glomeruli rich in cells containing hyperchromatic nuclei which were more intense in Exp9x. Regarding the fetal organs, no morphological or physiological changes were observed. A significant increase of AST (305.70±55.80, p<0.05) and creatinine (0.50±0.09, p<0.05) was observed in group Exp9x. CONCLUSIONS: our results show that the administration of the zidovudine, lamivudine and ritonavir combination to pregnant rats at high doses caused morphological and physiological changes in the maternal liver and kidneys. On the other hand, there were no changes in fetal organs.
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Animais , Feminino , Gravidez , Ratos , Fármacos Anti-HIV/farmacologia , Feto/anatomia & histologia , Feto/efeitos dos fármacos , Rim/anatomia & histologia , Rim/efeitos dos fármacos , Lamivudina/farmacologia , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Ritonavir/farmacologia , Zidovudina/farmacologia , Feto/patologia , Feto/fisiologia , Feto/fisiopatologia , Rim/patologia , Rim/fisiologia , Rim/fisiopatologia , Fígado/patologia , Fígado/fisiologia , Fígado/fisiopatologia , Ratos WistarRESUMO
Purpose: To evaluate the placental glycogen storage and fetal development in the pregnancy of neonatally streptozocin-induced diabetic rats and to establish relation with glycemia and insulin levels. Methods: At the birth day, 147 female rats were randomly distributed in two experimental groups: 1) Non-diabetic Group (Control, n=45) - received the vehicle; 2) Diabetic Group (STZ, n=102) - received 100 mg streptozocin/kg in neonatal period. At day 0 of pregnancy, adult female rats were included in the control group when presented glycemia below 120 mg/dL and, in the group STZ with glycemia between 120 and 300 mg/dL. At day 21 of pregnancy, blood samples were collected for glycemia and insulin determination, and placentas withdrawn for placental glycogen determination. The newborns (NB) were classified in small (SGA), appropriate (AGA) and large (LGA) for gestational age. Results: Rats STZ presented higher glycemia at days 0 and 14 of pregnancy. At end of pregnancy, rats STZ showed higher proportion of NB SGA and LGA; reduced rate of NB AGA and unaltered glycemia, insulin and placental glycogen determinations. Conclusion: Mild diabetes altered the maternal glycemia in the early pregnancy, impairing future fetal development, but it caused no alteration on insulin and placental glycogen determination, confirming that this glycemic intensity was insufficient to change glycogen metabolism.
Objetivo: Avaliar os estoques de glicogênio placentário e o desenvolvimento fetal na prenhez de ratas com diabete moderado induzido no período neonatal e relacionar com glicemia e níveis de insulina. Métodos: No dia de nascimento, foram distribuídas aleatoriamente 147 ratas em dois grupos experimentais: 1) Grupo Não-diabético (Controle, n=45) - recebeu o veículo; 2) Grupo Diabético (STZ, n=102) - recebeu 100 mg streptozocin/kg peso corpóreo. No dia 0 de prenhez, foram incluídas ratas controle que apresentassem glicemia baixo de 120 mg/dL e, no grupo STZ, com glicemia entre 120 e 300 mg/dL. No 21º dia de prenhez, amostras de sangue foram coletadas para glicemia e determinação de insulina e as placentas foram retiradas para determinação de glicogênio placentário. Os recém-nascidos (RN) foram classificados em pequeno (PIP), adequado (AIP) e grande (GIP) para idade de prenhez. Resultados: As ratas STZ apresentaram glicemias maiores nos dias 0 e 14 de prenhez. No final da prenhez, as ratas STZ mostraram maior proporção de RN PIP e GIP, taxa reduzida de RN AIP e inalteração em glicemia, insulina e na determinação de glicogênio placentário. Conclusão: O diabete moderado alterou a glicemia materna no início da prenhez, prejudicando o futuro desenvolvimento placentário e fetal, mas não causou nenhuma alteração na determinação de insulina e de glicogênio placentário, confirmando que esta intensidade de glicêmica foi insuficiente para modificar o metabolismo de glicogênio.
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Animais , Feminino , Masculino , Gravidez , Ratos , Diabetes Mellitus Experimental/metabolismo , Glicogênio/sangue , Insulina/sangue , Placenta/metabolismo , Gravidez em Diabéticas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Gravidez em Diabéticas/induzido quimicamente , Distribuição Aleatória , Ratos Wistar , Índice de Gravidade de Doença , EstreptozocinaRESUMO
OBJETIVO: avaliar o efeito da exposição de ratas ao ultra-som terapêutico na fase de pré-implantação. MÉTODOS: ratas Wistar prenhes foram expostas, na fase de pré-implantação, ao ultra-som de 3 MHz, 0,6 W/cm², com ondas pulsadas (USP) ou ondas contínuas (USC), e os controles (USS) ao ultra-som desligado, por cinco minutos. As ratas foram sacrificadas no 20º dia pós-inseminação. Foram feitas análises bioquímicas e hematológicas. Os animais foram submetidos à necrópsia para identificação de lesões de órgãos internos, remoção e pesagem de fígado, rins e ovários. Foram contados os fetos vivos, malformados, mortos e reabsorvidos. Os fetos, seus cérebros, pulmões, fígados, rins e placentas foram pesados. Os dados obtidos foram analisados por ANOVA - uma via - seguida de teste de Dunnett, qui quadrado ou Kruskal-Wallis (α = 0,05). RESULTADOS: as ratas não apresentaram alteração de peso corporal, de órgãos e nem na capacidade reprodutiva, mas houve o aumento dos triglicérides em ambos os grupos, quando comparados ao USS. Os pesos relativos do coração (0,7 ± 0,9), fígado (9,8 ± 0,8), rins (6,2 ± 0,8) e pulmão (3,8 ± 0,4) dos fetos aumentaram no USC, quando comparados ao coração (0,6 ± 0,1), fígado (8,8 ± 0,5), rins (5,52 ± 0,5) e pulmão (3,4 ± 0,4) do USS. CONCLUSÕES: no modelo experimental usado, o ultra-som terapêutico não causou toxicidade materna significativa. Ondas pulsadas não alteraram a morfologia fetal, mas as ondas contínuas acarretaram aumento nos pesos relativos do coração, fígado, pulmão e rins dos fetos.
PURPOSE: to evaluate the effect of exposure of female rats to therapeutic ultrasound in the pre-implantation phase. METHODS: pregnant Wistar female rats have been exposed to 3 MHz, 0.6 W/cm² ultrasound, pulsatile ultrasound (PUS) or continuous ultrasound (CUS), and controls, unplugged ultrasound (UUS), for five minutes. The rats were sacrificed at the 20th day post-insemination. Biochemical and hematological analyses have been done. Animals have been submitted to necropsy in order to identify lesions of internal organs, and to remove and weight the liver, kidneys and ovaries. Alive, malformed, dead and reabsorbed fetuses have been counted. RESULTS: the rats have not presented changes in their body and organs weight, and neither in their reproductive capacity, but there has been an increase in triglycerides in the PUS and CUS groups, when compared to the UUS group. The fetuses' relative weights of the heart (0.7 ± 0.9), liver (9.8 ± 0.8), kidneys (6.2 ± 0.8) and lungs (3.8 ± 0.4) increased in the CUS, when compared to the heart (0.7 ± 0.9), liver (9.8 ± 0.8), kidneys (6.2 ± 0.8) e lungs (3.8 ± 0.4) of the UUS. CONCLUSIONS: in the experimental model, the therapeutic ultrasound used has not caused meaningful maternal toxicity. Pulsatile waves have not changed fetal morphology, but continuous waves have caused increase in the relative weight of the fetuses' heart, liver, lungs and kidneys.
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Ratos , Animais , Blastocisto , Prenhez , Ratos Wistar , Terapia por UltrassomRESUMO
Objective To explore the effects of maternal hypercholanemia on the myocardium changes in rat fetus. Methods Thirty clean SD female rats were equally randomized to three groups after mating successfully.From the 13th to 20th day of gestation,group A and B were injected injected with sodium chloride(NS) as control.Total bile acid(TBA) and cardiac troponin I(cTnI) were measured in the maternal and fetal serum on the 21st day when all rats were killed.Fetal cardiac muscle cells were also collected for examination with light microscope and electronic microscope.Results (1)TBA in maternal and fetal serum were(22.32±8.12)μmol/L and(28.84±8.06) μmol/L,respectively in group A,(9.77±3.56)/μmol/L and(9.34±3.54) μmol/L in group B,and (3.60±1.78) μmol/L and(3.95±1.19) μmol/L in group C.Significant differences were found among groups(P<0.01).(2)Fetal death rates were significantly different among the three groups (P<0.05),with 30.11%,16.85%,and 7.05%,respectively.(3)Fetal cTnl were also found significant difference among groups(P<0.01),with(19.98±7.75)ng/ml,(11.41±3.64)ng/ml and(4.38±1.19)ng/ml,respectively.(4)The integrated scores of fetal necrosis area were significantly different in three groups(P<0.05),with 1.92±0.43,1.36±0.37 and 0.44±0.12,respectively.(5)Under electronic microscope,the number density of mitochondria in group A was lower than that in group C(P<0.05)while the average volume of mitochondria was larger in group A (P<0.05).The average volume of mitoehondria in group B was larger than that in group C(P<0.05) while no difference was found with regard to the number density between the two groups.The number density and average volume of myofibril in group A were lower than those in group C(P<0.05).The number density of myofibril in group B was higher than that in group C(P<0.05) while no difference was found with the average volume.(6)Positive correlations were found in maternal TBA,fetal TBA,fetal cTnI and the integrate of fetal necrosis area when comparing every two of the above factors. Conclusions Fetal myocardium is impaired obviously in hypercholanemia rats.The serum level of TBA and cTnI in fetal rats are positively correlated with each other.
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Diversos estudos epidemiológicos têm relacionado doenças na vida adulta, como diabetes tipo-2 e hipertensão, e ambiente inadequado durante a vida fetal. Fatores distintos relacionados aos hábitos alimentares, como ingestão de sal na dieta, podem ter impacto importante no período perinatal. Recentemente, demonstramos que dieta hipossódica (HO) durante a gestação está associada com baixo peso ao nascimento e alterações na vida adulta. O objetivo do presente estudo foi avaliar o efeito da dieta HO e hipersódica (HR) durante gestação em ratas. Ratas Wistar foram alimentadas com dieta HO, dieta normossódica ou HR desde a 8ª semana e foram acasaladas com 12 semanas de idade. Estes animais foram estudados na terceira semana de gestação e um grupo adicional de ratas virgens foi estudado como controle para o efeito da gestação. O peso da placenta e o do feto e o fluxo sanguíneo uterino foram menores e a resistência vascular periférica foi maior no grupo HO. Maior peroxidação lipídica e expressão gênica do receptor AT1 na placenta foram observadas no grupo HR. Em conclusão, peso do feto, peso da placenta e fluxo sanguíneo uterino são influenciados pelo consumo de sal durante a gestação.
Many epidemiological studies have linked diseases in adulthood, such as type-2 diabetes and hypertension, to adverse intrauterine environment during fetal life. Distinct factors related to dietary habits, such as salt intake, may have a major impact on the perinatal period. Recently, we have demonstrated that low-salt diet (LSD) during pregnancy is associated with low birth weight and diseases during adulthood. The aim of this study was to evaluate the effect of LSD and high-salt diet (HSD) during pregnancy in rats. Female Wistar rats were fed with LSD, normal-salt diet or HSD since 8 weeks of age and matted with 12 weeks of age. These animals were studied at the third week of gestation and one additional group of virgin rats was evaluated as a control for the gestation effect. Placenta and fetus weight and uterine blood flow were lower and peripheral vascular resistance was higher in the LSD group. In the placenta from HSD rats, higher lipid peroxidation and AT1 receptor mRNA were observed. In conclusion, fetal weight, placenta weight and uterine blood flow are influenced by the degree of salt consumption during pregnancy.
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Animais , Cobaias , Ratos , Placenta , Prenhez , Ratos Wistar , Fluxo Sanguíneo Regional , Sistema Renina-Angiotensina , SódioRESUMO
0.05). Conclusions Oxytocin, misoprostol or nimodipine can induce or inhibit labor through regulating expressions of VDCC L ? 1 and VDCC L ? 2 mRNA in the rat uterine myometrium and it may not have an adverse effect on heart function of normal pregnant rats. VDCC L may be the common channel of labor induced by internal or external factors.
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Objective To investigate the availability of early gestation termination with low frequency ultrasound.Methods The 10th day rabbit embryos were irradiated with low frequency focused ultrasound of 6 different levels of sound intensity.The rates of embryonic mortality were observed and the expression of p53 was detected by using immunohistochemistry 10 days after the irradiating.Results The rates of embryonic mortalities were 25.00%,72.88 % and 100% with the intensity of 30 W/cm~2,35 W/cm~2 and 40 W/cm~2 for 60 seconds,respectively.The expression of p53 in placenta cells increased after irradiating,peaked at 96 hours,and recovered to control level at 192 hours.Conclusion It is feasible for early pregnancy termination with low frequency ultrasound.The low frequency ultrasound may induce the increased expression of p53 in placenta cells,but the expression may be recovered.
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Objective To determine if pregnancy affects the toxicity of bupivacaine and to investigate the effect of Shenfu injectio,a preparation of Chinese herbal medicine,on central nervous system and cardiac toxicity of bupivacaine in pregnant rats.Methods Twenty-four SD rats weighing 320-360 g were assigned to 3 groups(n =8 each):Ⅰ non-pregnant control group,Ⅱ pregnant control group and Ⅲ Shenfu injectio pretreatment group. The animals were anesthetized with isoflorane(2%-4%)-O_2 inhalation which was stopped before bupivacaine infusion was started.Femoral artery was canunlated for MAP monitoring and blood sampling and femoral vein was cannulated for bupivacaine infusion.MAP,HR and ECG were continuously monitored.All animals in the 3 groups received continuous infusion of 5% bupivacaine at 2 mg?kg~(-1).min~(-1).In group Ⅲ Shenfu injectio 10 ml?kg~(-1) was injected intraperitoneally(IP)30 min before bupivacaine infusion whereas in the two control groups(group Ⅰ and Ⅱ)equal volume of normal saline was injected IP instead of Shenfu injectio.The duration between the beginning of bupivacaine infusion and onset of convulsion/arrhythmia(QRS≥90 ms)/asystol was recorded and the amount of bupivacaine infused was calculated.Results There was no significant difference in the amount of bupivacaine causing convulsion and asystol between group Ⅰ and Ⅱ but the amount of bupivacaine causing arrhythmia was significantly larger in group Ⅰ(non-pregnant) than in group Ⅱ(pregnant control group)(P＜0.05).The amount of bupivacaine causing convulsion,arrhythmia and asystole was significantly larger in Shenfu injectio pretreatment group(group Ⅲ)than in pregnant control group(group Ⅱ)(P＜0.05 or 0.01).Conclusion Bupivacaine- induced cardiotoxicity is increased in pregnant rats and Shenfu injectio pretreatment can reduce the systemic toxicity of bupivacaine in pregnant rats.
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Female Kunming mice (6-8 weeks old) were exposed to total body irradiation by of 6?10 4V/m EMP(electromagnetic pulse, EMP) for five times in 6-8th day of gestation(post pregnant irradiation), or became pregnant within 14 days (early conception after irradiation), or 14-28 days (late conception after irradiation) after irradiation. Pregnant mice were killed at 18th day. Teratological markers were analysed to evaluate the effect of EMP irradiation on pregnancy and offspring. The results showed that EMP irradiation caused no significant changes in maternal body weight gains, most of organ weight and organ/body weight ratio. But it caused significant shortening of tail length of live foetus. The offspring sex ratio was decreased after post pregnant irradiation and early conception after irradiation. Body weight was decreased in the early and late conception after irradiation. EMP irradiation also resulted in a significant increase in fetal death rate and embryo absorption rate compared with control group, especially in the late conception group, which was increased 5 2 and 3 8 times respectively. The results suggested that EMP irradiation exerted certain effects on pregnancy and offspring development in both pre pregnant and post pregnant female mice.
