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1.
Theriogenology ; 164: 58-64, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550092

RESUMO

Mammalian sperm is highly susceptible to reactive oxygen species (ROS) during the cryopreservation process. Astaxanthin (AST), a red pigment of the carotenoid family, is recognized as having a variety of beneficial biological activities and effects, including antioxidant, anticancer, anti-diabetic, and anti-inflammatory. The present study aimed to investigate whether the presence of AST protected boar sperm from ROS stress during cryopreservation. Boar sperm was diluted with a freezing medium supplemented with different concentrations of AST (0, 0.5, 1, 2, or 5 µM). The addition of AST, especially at a concentration of 2 µM, exerted positive effects on post-thaw sperm motility parameters. Meanwhile, sperm plasma membrane integrity and acrosome integrity of post-thaw sperm were significantly increased, while lipid peroxidation was inhibited in response to 2 µM AST treatment. Interestingly, compared to the control, supplementation with 2 µM AST increased unsaturated fatty acids (UFAs) levels and decreased saturated fatty acids (SFAs) content in post-thaw sperm, leading to a decreased ratio of SFAs/UFAs in the AST group. In conclusion, the addition of AST to freezing extenders inhibited lipid peroxidation and regulated fatty acid composition of the sperm membrane, improved post-thaw sperm quality, and had no adverse effect on boar sperm in vitro fertilization (IVF) capacity and potential for embryonic development. Our data provide a novel insight into understanding the mechanisms of AST concerning protecting boar sperm quality against ROS damage during cryopreservation.

2.
Anim Biotechnol ; : 1-11, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439093

RESUMO

The wedge-tailed green pigeon (Treron sphenurus) has a protective value in the evolution of the family Columbidae. In this study, the complete mitogenome of T. sphenurus from Baise City, China, which represents the first sequenced species of the genus Treron in Tribe Treronini, is reported. This was accomplished using PCR-based methods and a primer-walking sequencing strategy with genus-specific primers. The mitogenome was found to be 18,919 bp in length comprising 37 genes, including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and one control region. In terms of structure and composition, many similarities were found between the T. sphenurus and Hemiphaga novaeseelandiae (New Zealand pigeon) mitogenomes. This was further supported by phylogenetic analysis showing that T. sphenurus has a close evolutionary relationship with H. novaeseelandiae. The complete mitogenome of T. sphenurus reported here is expected to provide valuable molecular information for further studies on the phylogeny of the genus Treron and for analyses of the taxonomic status of the family Columbidae.

3.
Asian-Australas J Anim Sci ; 33(11): 1763-1769, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32054191

RESUMO

OBJECTIVE: This study was conducted to investigate the effect of L-carnitine on the pig semen characteristics during storage. METHODS: Spermatozoa samples were examined for spermatozoa quality and then randomly divided into 5 groups: 0 (control), 12.5, 25, 50, and 100 mM L-carnitine. Sperm motility, plasma membrane integrity and antioxidant parameters (total reactive oxygen species, total antioxidant capacity, and malondialdehyde) were evaluated after 0, 3, 5, and 10 day cooledstorage at 17°C. Moreover, ATP content, mitochondria activity as well as sperm-binding and in vitro fertilizing ability of preserved boar sperm were also investigated. RESULTS: Supplementation with 50 mM L-carnitine could effectively maintain boar sperm quality parameters such as sperm motility and membrane integrity. Besides, we found that L-carnitine had positive effects on boar sperm quality mainly through improving antioxidant capacities and enhancing ATP content and mitochondria activity. Interestingly, by assessing the effect of L-carnitine on sperm fertility and developmental potential, we discovered that the extender containing L-carnitine could improve sperm quality and increase the number of sperms bounding to zona pellucida, without improving in vitro fertility and development potential. CONCLUSION: These findings suggested that the proper addition of L-carnitine to the semen extender improved boar sperm quality during liquid storage at 17°C.

4.
Reprod Domest Anim ; 54(8): 1069-1077, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31099063

RESUMO

Spermatozoa are highly specialized cells, and energy metabolism plays an important role in modulating sperm viability and function. Rosiglitazone is an antidiabetic drug in the thiazolidinedione class that regulates metabolic flexibility and glucose uptake in various cell types, but its effects on boar sperm metabolism are unknown. In this study, we investigated the potential effect of rosiglitazone against time-dependent deterioration of boar spermatozoa during liquid preservation at 17°C. Freshly ejaculated semen was diluted with Beltsville Thawing Solution (BTS) containing different concentrations of rosiglitazone, and the motility, membrane and acrosome integrity of sperm were detected. Besides, we measured glucose uptake capacity, l-lactate production level, mitochondrial membrane potential, adenosine triphosphate (ATP) content and mitochondrial reactive oxygen species (mROS) production of sperm after boar semen had been incubated with or without rosiglitazone, iodoacetate (glycolysis inhibitor) and rotenone (electron transport chain inhibitor) for 5 days. The addition of rosiglitazone significantly enhanced sperm quality and had a strong protective effect on the sperm membrane and acrosome integrity during storage. BTS containing 50 µM rosiglitazone maintained the total motility of liquid-preserved sperm above 60% for 7 days. Rosiglitazone improved sperm quality by regulating energy metabolism manner of preserved sperm, protected the sperm mitochondrial membrane potential, enhanced sperm ATP production and in the meanwhile reduced mROS through enhancing glycolysis but not oxidative phosphorylation. The data suggested the practical feasibility of using rosiglitazone for improving boar spermatozoa quality during semen preservation.


Assuntos
Hipoglicemiantes/farmacologia , Rosiglitazona/farmacologia , Preservação do Sêmen/veterinária , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Suínos , Animais , Crioprotetores/farmacologia , Metabolismo Energético , Masculino , Motilidade Espermática
5.
Mil Med Res ; 4: 23, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28717517

RESUMO

BACKGROUND: Military medicine is a research field that seeks to solve the medical problems that occur in modern war conditions based on public medicine theory. METHODS: We explore the main research topics of military health and medical research in the web of science™ core collection (WoSCC) from 2007 to 2016, and the goal of this work is to serve as a reference for orientation and development in military health and medicine. Based on CiteSpace III, a reference co-citation analysis is performed for 7921 papers published in the WoSCC from 2007 to 2016. In addition, a cluster analysis of research topics is performed with a comprehensive analysis of high-yield authors, outstanding research institutions and their cooperative networks. RESULTS: Currently, the research topics in military health and medicine mainly focus on the following seven aspects: mental health diagnoses and interventions, an army study to assess risk and resilience in service members (STARRS), large-scale military action, brain science, veterans, soldier parents and children of wartime, and wound infection. We also observed that the annual publication rate increased with time. Wessely S, Greenberg N, Fear NT, Smith TC, Smith B, Jones N, Ryan MAK, Boyko EJ, Hull L, and Rona RJ were the top 10 authors in military health and medicine research. The top 10 institutes were the Uniformed Services University of the Health Sciences, the United States Army, the United States Navy, Kings College London, Walter Reed National Military Medical Center, Boston University, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Naval Health Research Center, and the VA Boston Healthcare System. CONCLUSIONS: We are able to perform a comprehensive analysis of studies in military health and medicine research and summarize the current research climate and the developmental trends in the WoSCC. However, further studies and collaborations are needed worldwide. Overall, our findings provide valuable information and new perspectives and shape future research directions for further research in the area of military health and medicine.


Assuntos
Bases de Conhecimento , Medicina Militar/métodos , Pesquisa/história , História do Século XXI , Humanos , Medicina Militar/educação , Publicações/tendências , Saúde dos Veteranos/tendências
6.
Sci Rep ; 6: 26807, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27226238

RESUMO

This study was designed to investigate the effect of U50,488H (a selective κ-opioid receptor agonist) on endothelial function impaired by hyperlipidemia and to determine the role of Akt-stimulated NO production in it. Hyperlipidemic model was established by feeding rats with a high-fat diet for 14 weeks. U50,488H and nor-BNI (a selective κ-opioid receptor antagonist) were administered intraperitoneally. In vitro, the involvement of the PI3K/Akt/eNOS pathway in the effect of U50,488H was studied using cultured endothelial cells subjected to artificial hyperlipidemia. Serum total cholesterol and low-density lipoprotein cholesterol concentrations dramatically increased after high-fat diet feeding. Administration of U50,488H significantly alleviated endothelial ultrastructural destruction and endothelium-dependent vasorelaxation impairment caused by hyperlipidemia. U50,488H also increased Akt/eNOS phosphorylation and serum/medium NO level both in vivo and in vitro. U50,488H increased eNOS activity and suppressed iNOS activity in vivo. The effects of U50,488H were abolished in vitro by siRNAs targeting κ-opioid receptor and Akt or PI3K/Akt/eNOS inhibitors. All effects of U50,488H were blocked by nor-BNI. These results demonstrate that κ-opioid receptor stimulation normalizes endothelial ultrastructure and function under hyperlipidemic condition. Its mechanism is related to the preservation of eNOS phosphorylation through activation of the PI3K/Akt signaling pathway and downregulation of iNOS expression/activity.


Assuntos
Células Endoteliais/efeitos dos fármacos , Hiperlipidemias/metabolismo , Óxido Nítrico/biossíntese , Proteínas Proto-Oncogênicas c-akt/fisiologia , Receptores Opioides kappa/fisiologia , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/ultraestrutura , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Óxido Nítrico Sintase/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
7.
Am J Ther ; 20(5): 493-501, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23011166

RESUMO

κ-opioid receptor (κ-OR) activation with U50,488H, a selective κ-OR agonist, has been previously demonstrated to prevent against cardiac arrhythmias via stabilizing the synthesis and degradation of an integral membrane protein, Cx43, in gap junctions. However, the exact prevention mechanism remains unclear. The present study tested the hypothesis that the kappa OR agonist U50,488H mediates the prevention of arrhythmia through the regulation of intracellular calcium leading to the preservation of Cx43 protein. By performing electrocardiogram monitoring and immunoblotting in isolated Langendorff-perfused rat hearts, high concentrations of calcium-perfused rat hearts exhibited increased cardiac arrhythmias. Diminished expression of Cx43 protein was observed. The utilization of a whole-cell patch clamp technique revealed that U50,488H inhibited L-type calcium current in single ventricular myocytes in a dose-dependent manner. These effects were blocked by nor-binaltorphimine, potent and selective κ-OR antagonists. Administration of U50,488H before myocardial ischemia resulted in an attenuated of total arrhythmia scores. The attenuation effect was blocked by nor-binaltorphimine. The attenuation effect was antagonized both by Bay K8644, a L-type calcium channel agonist, and also by the Cx43 uncoupler heptanol. Finally, immunoblotting data demonstrated that the preservation of Cx43 protein conferred by U50,488H was reversed in the presence of Bay K8644. In summary, the present study demonstrates κ-OR activation with U50,488H may confer antiarrhythmic effects via modulation of the calcium-Cx43 pathway.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Anti-Hipertensivos/farmacologia , Arritmias Cardíacas/prevenção & controle , Conexina 43/metabolismo , Receptores Opioides kappa/agonistas , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Cálcio/metabolismo , Agonistas dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Masculino , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/antagonistas & inibidores
8.
Biochim Biophys Acta ; 1832(1): 128-41, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22967841

RESUMO

Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+) exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Apoptose , Cardiomiopatias/fisiopatologia , Citocromo P-450 CYP2E1/metabolismo , Regulação para Baixo , Contração Miocárdica , Miócitos Cardíacos/fisiologia , Animais , Cardiomiopatias/complicações , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Células Cultivadas , Citocromo P-450 CYP2E1/genética , Inibidores do Citocromo P-450 CYP2E1 , Etanol/efeitos adversos , Etanol/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo
9.
J Appl Physiol (1985) ; 114(2): 238-44, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23139366

RESUMO

Impairment of pulmonary endothelium function in the pulmonary artery is a direct result of chronic hypoxia. This study is to investigate the vasculoprotective effects of U50,488H (a selective κ-opioid receptor agonist) and its underlying mechanism in hypoxia-induced pulmonary artery endothelial functional injury. Chronic hypoxia was simulated by exposing the rats to 10% oxygen for 2 wk. After hypoxia, right ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI) were measured. The pulmonary vascular dysfunction, effect of nitric oxide synthase inhibitor (l-NAME) on the relaxation of U50,488H, and level of nitric oxide (NO) were determined. In vitro, the signaling pathway involved in the anti-apoptotic effect of U50,488H was investigated. Cultured endothelial cells were subjected to simulated hypoxia, and cell apoptosis was determined by TUNEL staining. U50,488H (1.25 mg/kg) significantly reduced RVP and RVHI in hypoxia. U50,488H markedly improved both pulmonary endothelial function (maximal vasorelaxation in response to ACh: 74.9 ± 1.8%, n = 6, P <0.01 vs. hypoxia for 2 wk group) and increased total NO production (1.65 fold). U50,488H relaxed the pulmonary artery rings of the hypoxic rats. This effect was partly abolished by l-NAME. In cells, U50,488H both increased NO production and reduced hypoxia-induced apoptosis. Moreover, pretreatment with nor-binaltorphimine (nor-BNI, a selective κ-opioid receptor antagonist), PI3K inhibitor, Akt inhibitor or l-NAME almost abolished anti-apoptotic effect exerted by U50,488H. U50,488H resulted in increases in Akt and eNOS phosphorylation. These results demonstrate that pretreatment with U50,488H attenuates hypoxia-induced pulmonary vascular endothelial dysfunction in an Akt-dependent and NO-mediated fashion.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Endotélio Vascular/efeitos dos fármacos , Hipóxia/metabolismo , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Opioides kappa/agonistas , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Técnicas In Vitro , Masculino , Modelos Animais , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Artéria Pulmonar/citologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/antagonistas & inibidores
10.
PLoS One ; 7(12): e51223, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23284668

RESUMO

This study was designed to investigate whether Resveratrol (Res) could be a prophylactic factor in the prevention of I/R injury and to shed light on its underlying mechanism. Primary culture of neonatal rat cardiomyocytes were randomly distributed into three groups: the normal group (cultured cardiomyocytes were in normal conditions), the I/R group (cultured cardiomyocytes were subjected to 2 h simulated ischemia followed by 4 h reperfusion), and the Res+I/R group (100 µmol/L Res was administered before cardiomyocytes were subjected to 2 h simulated ischemia followed by 4 h reperfusion). To test the extent of cardiomyocyte injury, several indices were detected including cell viability, LDH activity, Na(+)-K(+)-ATPase and Ca(2+)-ATPase activity. To test apoptotic cell death, caspase-3 activity and the expression of Bcl-2/Bax were detected. To explore the underlying mechanism, several inhibitors, intracellular calcium, SOD activity and MDA content were used to identify some key molecules involved. Res increased cell viability, Na(+)-K(+)-ATPase and Ca(2+)-ATPase activity, Bcl-2 expression, and SOD level. While LDH activity, capase-3 activity, Bax expression, intracellular calcium and MDA content were decreased by Res. And the effect of Res was blocked completely by either L-NAME (an eNOS inhibitor) or MB (a cGMP inhibitor), and partly by either DS (a PKC inhibitor) or Glybenclamide (a K(ATP) inhibitor). Our results suggest that Res attenuates I/R injury in cardiomyocytes by preventing cell apoptosis, decreasing LDH release and increasing ATPase activity. NO, cGMP, PKC and K(ATP) may play an important role in the protective role of Res. Moreover, Res enhances the capacity of anti-oxygen free radical and alleviates intracellular calcium overload in cardiomyocytes.


Assuntos
Cardiotônicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Estilbenos/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , L-Lactato Desidrogenase/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Resveratrol , ATPase Trocadora de Sódio-Potássio/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
Mol Biol Rep ; 39(4): 3837-45, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21773950

RESUMO

Transcription factor RBP-J-mediated Notch signaling has been implicated in several inherited cardiovascular diseases including aortic valve diseases (AVD). But whether Notch signal plays a role in AVD in adults has been unclear. This study aims to test whether the deletion of RBP-J in adult mice would lead to AVD and to investigate the underlying mechanisms. Cre-LoxP-mediated gene deletion was employed to disrupt Notch signal in adult mice. Immunofluorescence and electron microscope observations showed that deletion of RBP-J in adult mice led to early morphological changes of AVD. The size of aortic valve was enlarged. The endothelial homeostasis was perturbed, probably due to the up-regulation of VEGFR2. The endothelial cells exhibited increased proliferation and loose endothelial junctions. The valvular mesenchyme displayed significant fibrosis, consistent with the up-regulation of TGF-ß1 and activation of endothelial-mesenchymal transition. We observed melanin-producing cells in aortic valves. The number of melanin-producing cells increased significantly, and their location changed from the mesenchyme to subendothelial layer of valve cusps in RBP-J deficient mice. These results suggest that RBP-J-mediated Notch signaling in aortic valves may be critically involved in valve homeostasis and valve diseases as well. These findings will be helpful for the understanding of the molecular mechanisms of AVD in adults.


Assuntos
Envelhecimento/patologia , Valva Aórtica/patologia , Deleção de Genes , Doenças das Valvas Cardíacas/patologia , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/deficiência , Animais , Valva Aórtica/anormalidades , Valva Aórtica/ultraestrutura , Cardiomegalia/complicações , Cardiomegalia/patologia , Proliferação de Células , Endotélio/patologia , Doenças das Valvas Cardíacas/complicações , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Melaninas/metabolismo , Mesoderma/patologia , Camundongos , Camundongos Knockout , Regulação para Cima , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
12.
Huan Jing Ke Xue ; 32(7): 1994-9, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21922820

RESUMO

To further know the seasonal variation characteristics of phosphorus species in lake sediment, the contents of different phosphorus species in the surface sediment sampling from Changshou Lake were determined by using the SMT sequential extraction method in July and November, 2009, and March, 2010. The contents of total phosphorus (TP) basically show an order of the low-water period, high-water period, and normal-water period from high to low, and the maximum appeared in Shoudao (2960.29 mg/kg) while the minimum in Guanjiakou (586.05 mg/kg). The mass fractions of phosphorus associated with hydrous ferric/aluminum oxides (Fe/Al-P) and organic phosphorus (OP) in TP at all sampling sits are in an order of the normal-water period, high-water period, and low-water period from high to low, and the maximum of Fe/Al-P appeared in Lewen (40.01%) while that of OP in the dam mouth (72.44%). The mass fraction of phosphorus bound to calcium salt (Ca-P) in TP is in an order of the low-water period, normal-water period, and high-water period, and the maximum appeared in Baibudang (15.52%). These results suggested that the phosphorus speciation in the sediment of Changshou Lake shows obviously temporal and spatial distribution characteristics, and Fe/Al-P is mainly influenced by pH of the overlying water, while OP is not apparently influenced by dissolved oxygen (DO).


Assuntos
Sedimentos Geológicos/química , Fósforo/química , Estações do Ano , Poluentes Químicos da Água/química , China , Monitoramento Ambiental , Água Doce/análise , Organofosfatos/química
13.
J Cardiovasc Pharmacol ; 58(2): 207-15, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21654505

RESUMO

The aim of this study was to investigate the underlying mechanism that dynorphin, an endogenous kappa opioid receptor (κ-OR) agonist, triggers antiapoptotic effect of postconditioning (Postcon). In addition to vehicle treatment, Sprague Dawley rats (n = 6) underwent a 30-minute left anterior descending occlusion followed by 2 hours of reperfusion with or without a Postcon stimulus. The selective κ-OR antagonist nor-binaltorphimine (Nor-BNI) was administered intravenously 5 minutes before reperfusion. Infarct size was determined by using 2,3,5-triphenyltetrazolium chloride staining. Blood plasma concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH) and myocardial caspase-3 activity were analyzed spectrophotometrically. Myocardial apoptosis was analyzed by the detection of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling. Immunoreactive dynorphin in blood serum and myocardium was measured by means of an antigen-competitive enzyme-linked immunosorbent assay. Infarction size, caspase-3 activity, apoptotic index, and CK and LDH levels were significantly higher in the ischemic/reperfusion group than in the vehicle group (P < 0.01). Postcon significantly reduced infarction size, caspase-3 activity, apoptotic index, CK and LDH levels (P < 0.01 vs. ischemic/reperfusion). Dynorphin content significantly increased after Postcon (P < 0.01). All the effects described above were abolished by Nor-BNI, with the exception of dynorphin content. We found that cardiac protection and antiapoptotic effect of Postcon is mediated by the activation of κ-OR. Effect of Postcon is mediated, at least partially, by enhanced dynorphin expression.


Assuntos
Apoptose , Dinorfinas/metabolismo , Pós-Condicionamento Isquêmico , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Receptores Opioides kappa/agonistas , Animais , Modelos Animais de Doenças , Dinorfinas/sangue , Hemodinâmica , Marcação In Situ das Extremidades Cortadas , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Sprague-Dawley
14.
Crit Care Med ; 38(12): 2365-76, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20890194

RESUMO

OBJECTIVE: Acute myocardial ischemia induces electrical and chemical uncoupling of gap junctions, which contributes to conduction abnormalities and re-entrant arrhythmias. We tested the hypothesis that structure and function of Connexin43 may vibrate during acute myocardial ischemia and reperfusion and κ-opioid receptor stimulation may stabilize the alteration of Connexin43. DESIGN: An animal intervention study was conducted with comparison to a control group. SETTING: University preclinical research laboratory. SUBJECTS: Age-, weight-, and sex-matched Sprague-Dawley rats. INTERVENTIONS: Adult rat hearts were subjected to ischemia or ischemia/reperfusion, which was induced by temporary occlusion of the left main coronary artery. U50488H was given 10 mins before tissue specimens were taken or before ischemia (1.5 mg/kg, intravenous) and nor-BNI was given 15 mins before tissue specimens were taken or before ischemia (2 mg/kg, intravenous). Tissue samples came from left ventricular myocardium of the rat hearts. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram, immunohistochemistry, immunoblotting, and reverse transcription-polymerase chain reaction were used to measure changes of arrhythmias, protein, and gene expression of Connexin43, respectively. κ-opioid receptor activation with U50 decreased arrhythmia in a model of myocardial ischemia and reperfusion. In normal hearts, immunohistochemical data showed reduced amount and lateralization of Connexin43 induced by κ-opioid receptor activation, whereas immunoblotting data demonstrated no significant changes between control and U50 group. During ischemia, however, Connexin43 protein underwent dephosphorylation and degradation, and Connexin43 mRNA was upregulated. These alterations were significantly attenuated on κ-opioid receptor stimulation. During ischemia and reperfusion, Connexin43 protein underwent dephosphorylation and degradation and recovered slowly during reperfusion. Activation of κ-opioid receptor accelerated recovery of phosphorylated and total Connexin43. CONCLUSIONS: In normal rat hearts, Connexin43 translocates from intercellular junctions to intracellular locations on κ-opioid receptor activation. In rat hearts experiencing acute myocardial ischemia and reperfusion, protein and gene expression of Connexin43 undergo vibration. This phenomenon is stabilized when κ-opioid receptor is activated and by the fact that κ-opioid receptor produces antiarrhythmic effects.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Conexina 43/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptores Opioides kappa/metabolismo , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/metabolismo , Animais , Arritmias Cardíacas/fisiopatologia , Western Blotting , Conexina 43/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Junções Comunicantes/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
J Appl Physiol (1985) ; 108(4): 838-44, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20133438

RESUMO

Modulation of intracellular calcium ([Ca(2+)](i)) transient in response to beta-adrenoceptor stimulation in the hearts of hindlimb unweighted (HLU) rats during simulated weightlessness has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness. Effects of simulated microgravity on beta-adrenoceptor responsiveness were then studied. Mean arterial blood pressure, left ventricular pressure (LVP), systolic function [maximum positive change in pressure over time (+dP/dt(max))], and diastolic function [maximum negative change in pressure over time (-dP/dt(max))] were monitored during the in vivo experiment. beta-Adrenoceptor density was quantitated by radioactive ligand binding. Single rat ventricular myocyte was obtained by enzymatic dissociation method. +/-dP/dt(max), myocyte contraction, intracellular [Ca(2+)](i) transient, and L-type calcium current in response to beta-adrenoceptor stimulation with isoproterenol were measured. Compared with the control group, no significant changes were found in heart weight, body weight, and mean arterial blood pressure, whereas LVP and +/-dP/dt(max) were significantly reduced. LVP and +/-dP/dt(max) were significantly attenuated in the HLU group in response to isoproterenol administration. In the in vitro study, the beta-adrenoceptor density was unchanged. Effects of isoproterenol on electrically induced single-cell contraction and [Ca(2+)](i) transient in myocytes of ventricles in HLU rats were significantly attenuated. The enhanced L-type Ca(2+) current elicited by isoproterenol in cardiomyocytes was significantly decreased in the HLU group. The above results indicate that impaired function of L-type Ca(2+) current and decreased [Ca(2+)](i) transient cause the depressed responsiveness of the beta-adrenoceptor stimulation, which may be partially responsible for the depression of cardiac function.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Coração/efeitos dos fármacos , Elevação dos Membros Posteriores , Isoproterenol/farmacologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/fisiologia , Sinalização do Cálcio/fisiologia , Coração/fisiologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Hemodinâmica/efeitos dos fármacos , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Arch Med Res ; 40(4): 227-34, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19608010

RESUMO

BACKGROUND AND AIMS: It remains unclear whether U50488H (a selective kappa-opioid receptor agonist) produces anti-apoptotic effect during ischemia and reperfusion (I/R). Therefore, the effect of U50488H on myocardial apoptosis was investigated in the present study. METHODS: Rats were subjected to 45min coronary artery occlusion and 180min of reperfusion. U50488H (1.5mg/kg IV) was given prior to occlusion. Nor-Binaltorphimine (nor-BNI) (2mg/kg IV), a selective kappa-opioid receptor antagonist, was given 10min prior to U50488H. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay and in situ identification of nuclear DNA fragmentation. RESULTS: The ultrastructure injury of myocardium, myocardial infarct size, and plasma CK and LDH were reduced significantly with administration of U50488H before I/R, whereas the effects of U50488H were abolished by nor-BNI. DNA fragments were visualized by agarose electrophoresis, and clear DNA ladder formation was observed in myocardial tissue from hearts subjected to I/R. Administration of U50488H before ischemia exerted a significant anti-apoptotic effect as evidenced by markedly weaker DNA ladder formation. TUNEL staining showed U50488H treatment before I/R significantly reduced the percentage of apoptotic cells, which was blocked by 5-HD, a mitochondrial k(ATP) channel blocker. In accordance, U50488H treatment significantly inhibited I/R-induced elevated activities of caspase-3 and caspase-9. U50488H also produced an increase in Bcl-2 and a decrease in Bax protein expression in the I/R heart, and the anti-apoptotic effects of U50488H were all blocked by nor-BNI. CONCLUSIONS: U50488H reduces myocardial necrosis and apoptosis after I/R and activation of kappa-opioid receptor may mediate a role in U50488H-induced myocardial protection.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/uso terapêutico , Apoptose/efeitos dos fármacos , Infarto do Miocárdio/prevenção & controle , Receptores Opioides kappa/agonistas , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Hipertensivos/farmacologia , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/efeitos dos fármacos , Caspase 9/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Masculino , Microscopia Eletrônica de Transmissão , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
17.
Vascul Pharmacol ; 51(2-3): 72-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19351568

RESUMO

The aim of the present study was to determine whether U50,488H, a selective kappa-opioid receptor agonist, inhibits the remodeling of the pulmonary artery (PA). In addition, changes in the concentrations of nitric oxide (NO), endothelin (ET) and angiotensin II (AngII) in hypoxic pulmonary hypertensive (HPH) rats were investigated to explore the mechanisms underlying the effects of U50, 488H on HPH. We found that intraperitoneal administration of U50,488H (every other day) during hypoxia depressed mean pulmonary arterial pressure (mPAP) and attenuated right ventricular pressure (RVP) and right ventricular hypertrophy, at the same time it inhibited remodeling of the PA compared with hypoxia for 2 wk. Moreover, U50,488H also inhibited proliferation of the pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia for 48 h in a dose-dependent manner. Compared with the 2 wk hypoxia group, U50,488H increased the concentration of NO and decreased the production of ET and AngII (P<0.01). In addition, acute intravenous administration of U50,488H after hypoxia for 4 wk decreased mPAP. Our results suggest that effects of anti-remodeling of the PA and anti-proliferation of the PASMC, and regulation of the vasomotor factors in both blood and pulmonary tissues of HPH rats may be critical mechanisms underlying the preventive and therapeutic effects of U50,488H in HPH rats.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/prevenção & controle , Hipóxia/tratamento farmacológico , Oxigênio/fisiologia , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/administração & dosagem , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/uso terapêutico , Análise de Variância , Angiotensina II/análise , Angiotensina II/sangue , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Câmaras de Exposição Atmosférica , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Doença Crônica/prevenção & controle , Modelos Animais de Doenças , Endotelinas/análise , Endotelinas/sangue , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Hipóxia/fisiopatologia , Injeções Intraperitoneais , Pulmão/química , Pulmão/efeitos dos fármacos , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Óxido Nítrico/análise , Óxido Nítrico/sangue , Tamanho do Órgão/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/agonistas , Fatores de Tempo
18.
Eur J Pharmacol ; 607(1-3): 135-42, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19233160

RESUMO

The aim of the present study was to determine whether U50,488H (a selective kappa-opioid receptor agonist) inhibits cardiac hypertrophy and fibrosis induced by beta-adrenoceptor stimulation in a rat model. Cardiac hypertrophy and fibrosis were developed by intraperitoneal administration of isoprenaline (ip. 3.0 mg/kg/day,14 days). In the isoprenaline-treated group, heart weight and heart-to-body ratio increased significantly. Hypertrophic alterations were observed in light micrographs of tissue and transmission electron micrographs of myocardial ultra structures. Increases in heart weight, heart-to-body ratio, diameter of cardiomyocytes, and morphological hypertrophic alterations induced by isoprenaline were significantly attenuated by U50,488H(i.p. 1.25 mg/kg/day). Growth of cardiomyocytes was induced by incubating with isoprenaline (10(-6) mol/l), which resulted in an increase in optical density (OD) values. The increased OD value was attenuated by U50,488H(10(-7) mol/l-10(-5) mol/l) in a dose dependent manner. Animals receiving administration of isoprenaline displayed significant fibrosis. The extent of isoprenaline induced left ventricular fibrosis was dramatically reduced in U50,488H treated animals. Increased cardiac fibroblast proliferation and collagen synthesis induced by isoprenaline, as evidenced by increased OD value, (3)H-thymidine, and (3)H-proline incorporation, were significantly reduced in the U50,488H treated group. The specific extracellular matrix proteins, including type I, type III collagen and fibronectin, which increased after administration of isoproterenol, were also attenuated by U50,488H. The abovementioned effects of U50,488H were completely abolished by nor-BNI (nor-binaltorphimine), a selective kappa-opioid receptor antagonist. The enhanced intracellular Ca(2+) transient and L-type Ca(2+) current elicited by isoprenaline in cardiomyocytes were significantly inhibited by U50,488H. This study provides the first morphological evidence of the inhibitory effect of U50,488H on isoprenaline-induced cardiac hypertrophy and fibrosis via kappa-opioid receptor stimulation.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Cardiomegalia/prevenção & controle , Fibrose/prevenção & controle , Receptores Opioides kappa/agonistas , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/administração & dosagem , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Cálcio/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Cardiomegalia/fisiopatologia , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo III/efeitos dos fármacos , Colágeno Tipo III/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibronectinas/efeitos dos fármacos , Fibronectinas/metabolismo , Fibrose/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Isoproterenol , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley
19.
J Appl Physiol (1985) ; 105(2): 569-74, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18511523

RESUMO

The modulation of beta-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on beta-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dP/dtmax), and diastolic function (-dP/dtmax) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to beta-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and +/-dP/dtmax were significantly reduced. The ABP decrease, LVP increase, and +/-dP/dtmax in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced single-cell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gsalpha (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes beta-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.


Assuntos
Coração/fisiologia , Receptores Adrenérgicos beta/fisiologia , Transdução de Sinais/fisiologia , Simulação de Ausência de Peso , Adenilil Ciclases/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Anestesia , Animais , Peso Corporal/fisiologia , Colforsina/farmacologia , AMP Cíclico/metabolismo , Estimulação Elétrica , Elevação dos Membros Posteriores/fisiologia , Isoproterenol/farmacologia , Masculino , Contração Muscular/fisiologia , Contração Miocárdica/fisiologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Tamanho do Órgão/fisiologia , Ratos , Ratos Sprague-Dawley
20.
Arch Med Res ; 39(1): 45-51, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18067995

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a chronic disease characterized by loss of myelin. However, data indicate that autoimmune cells could directly impair neuronal cell bodies and myelin sheath is lacking. The aim of the present study was to determine morphological evidence of the direct impairment of neurons by autoreactive lymphocytes and to further identify the subtypes of these lymphocytes. METHODS: Lymphocytes activated by myelin basic protein (MBP) 83-99 and neurons of human brain were co-cultured for 24 h. RESULTS: Observations through scanning electron microscope showed that MBP-specific lymphocytes (CD4+, CD8+ cells, and NK cells) aggregated in the vicinity of the neuronal cell bodies and the myelin sheaths and attacked them directly, resulting in the degeneration of both neurons. CONCLUSIONS: Our studies provide morphological evidences of the direct impairment of neuronal cell bodies and myelin sheaths by MBP-specific lymphocytes. Our studies also suggest that MBP-specific CD4+, CD8+, and NK cells might be involved in this process. These processes may play a role in the direct impairment of neurons and myelin sheaths in early stages of MS and provide evidences for the application of immunosuppressant therapy of MS.


Assuntos
Células Matadoras Naturais/imunologia , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Bainha de Mielina/imunologia , Neurônios/imunologia , Adulto , Antígenos CD4/análise , Antígenos CD8/análise , Técnicas de Cocultura , Feminino , Humanos , Células Matadoras Naturais/classificação , Células Matadoras Naturais/ultraestrutura , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Proteína Básica da Mielina/análise , Bainha de Mielina/ultraestrutura , Neurônios/ultraestrutura , Fragmentos de Peptídeos/imunologia
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