RESUMO
Choroidal neovascularization (CNV) is a hallmark of wet age-related macular degeneration, which severely impairs central vision. Studies have shown that endothelial-mesenchymal transition (EndMT) is involved in the pathogenesis of CNV. Licochalcone A (lico A), a flavonoid extracted from the root of licorice, shows the inhibition on EndMT, but it remains unclear whether it can suppress the formation of CNV. The aim of this study is to investigate the effects of lico A on laser-induced CNV, and EndMT process in vitro and vivo. We established the model of CNV with a krypton laser in Brown-Norway rats and then intraperitoneally injected lico A. Our experimental results demonstrated that the leakage of CNV was relieved, and the area of CNV was reduced in lico A-treated rats. Cell migration and tube formation in oxidized low-density lipoprotein (Ox-LDL)-stimulated HUVECs were inhibited by lico A and promoted by PI3K activator 740Y-P. The protein expressions of snai1 and α-SMA were increased, and CD31 and VE-cadherin were decreased in the model rats of CNV, but partially reversed after treatment with lico A. The expression of CD31 was decreased and α-SMA was increased in OX-LDL-treated HUVECs, which was further strengthened by 740Y-P, while the expression of CD31 was up-regulated and α-SMA was down-regulated in lico A treated HUVECs. Our data revealed that EndMT process was alleviated by lico A. Meanwhile, PI3K/AKT signaling pathway was activated in model rat of CNV and Ox-LDL-stimulated HUVECs, which can be suppressed with treatment of lico A. Our experimental results confirmed for the first time that lico A has the potential to alleviate CNV by inhibiting the endothelial-mesenchymal transition via PI3K/AKT signaling pathway.
Assuntos
Neovascularização de Coroide , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/fisiologia , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/prevenção & controle , Neovascularização de Coroide/etiologia , Lasers , Ratos Endogâmicos BNRESUMO
As highly social animals, Indo-Pacific humpback dolphins ( Sousa chinensis) exhibit community differentiation. Nevertheless, our understanding of the external and internal factors influencing these dynamics, as well as their spatiotemporal variations, is still limited. In the present study, variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay, China, were monitored over two distinct periods (2007-2010 and 2017-2019) to analyze the effects of habitat utilization and the composition of individuals within the population. In both periods, the population demonstrated a strikingly similar pattern of social differentiation, characterized by the division of individuals into two main clusters and one small cluster. Spatially, the two primary clusters occupied the eastern and western waters, respectively, although the core distribution area of the eastern cluster shifted further eastward between the two periods. Despite this distribution shift, the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected. A subset of 16 individuals observed in both periods, comprising 51.6% and 43.2% of the population in each respective period, emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability, especially during the 2007-2010 period. These observations suggest that the composition of dominant individuals, an internal factor, had a more substantial influence on the formation of the social network than changes in habitat use, an external factor. Consequently, the study proposes distinct conservation measures tailored to each of the two main clusters.
Assuntos
Golfinhos , Animais , Ecossistema , ChinaRESUMO
OBJECTIVE: To investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells. METHODS: Fifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01). CONCLUSIONS: Extract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Luteína/farmacologia , Degeneração Macular/prevenção & controle , Xantofilas/farmacologia , Animais , Catepsina B/metabolismo , Cistatina C/metabolismo , Feminino , Peróxido de Hidrogênio , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado Ocular/efeitos dos fármacos , Epitélio Pigmentado Ocular/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , ZeaxantinasRESUMO
OBJECTIVE: To observe the protection of carbon monoxide (CO) inhalation on lipopolysaccharide (LPS)-induced rat multiple organ injury. METHODS: Sprague-Dawley rats with multiple organ injury induced by 5 mg/kg LPS intravenous injection were exposed to room air or 2. 5 x 10(-4) (V/V) CO for 3 hours. The lung and intestine tissues of rats were harvested to measure the expression of heme oxygenase-1 (HO-1) with reverse transcription-polymerase chain reaction, the levels of pulmonary tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and intestinal platelet activator factor (PAF), intercellular adhesion molecule-1 (ICAM-1) with enzyme-linked immunosorbent assay, the content of maleic dialdehyde (MDA) and the activity of myeloperoxidase (MPO) with chemical method, the cell apoptosis rate with flow cytometry, and the pathological changes with light microscope. RESULTS: CO inhalation obviously up-regulated the expression of HO-1 in lung (5.43 +/- 0.92) and intestine (6.29 +/- 1.56) in LPS + CO group compared with (3.08 +/- 0.82) and (3.97 +/- 1.16) in LPS group (both P < 0.05). The levels of TNF-alpha, IL-6 in lung and PAF, ICAM-1 in intestine of LPS + CO group were 0.91 +/- 0.25, 0.64 +/- 0.05, 1.19 +/- 0.52, and 1.83 +/- 0.35 pg/mg, respectively, significantly lower than the corresponding values in LPS group (1.48 +/- 0.23, 1.16 +/- 0.26, 1.84 +/- 0.73, and 3.48 +/- 0.36 pg/mg, all P < 0.05). The levels of MDA, MPO, and cell apoptosis rate in lung and intestine of LPS + CO group were 1.02 +/- 0.23 nmol/mg, 1.74 +/- 0.17 nmol/mg, 7.18 +/- 1.62 U/mg, 6.30 +/- 0.97 U/mg, 1.60% +/- 0.34%, and 30. 56% +/- 6.33%, respectively, significantly lower than the corresponding values in LPS group (1.27 +/- 0.33 nmol/mg, 2.75 +/- 0.39 nmol/mg, 8.16 +/- 1.49 U/mg, 7.72 +/- 1.07 U/mg, 3.18% +/- 0.51%, and 41.52% +/- 3.36%, all P < 0.05). In addition, injury of lung and intestine induced by LPS was attenuated at presence of CO inhalation. CONCLUSION: CO inhalation protects rat lung and intestine from LPS-induced injury via anti-oxidantion, anti-inflammation, anti-apoptosis, and up-regulation of HO-1 expression.
Assuntos
Monóxido de Carbono/administração & dosagem , Lipopolissacarídeos/toxicidade , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Animais , Sequência de Bases , Primers do DNA , Exposição por Inalação , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Carbon monoxide (CO), a metabolite of heme catalysis by heme oxygenase (HO), has been proposed to have anti-oxidative, anti-inflammatory and anti-apoptotic functions. Lipopolysaccharide (LPS)-induced lung injury (LI) is characterized by oxidative stress, inflammatory reaction and excessive pulmonary cell apoptosis. So we supposed that CO might have protection against LI. LI in rats was induced by intravenous injection of LPS (5 mg/kg). To observe the effect of CO inhalation, LI rats were exposed to 2.5 x 10(-4) (V/V) CO for 3 h. CO-induced changes of lung oxidative stress parameters, inflammatory cytokines, cell apoptosis, HO-1 expression and histology were examined. Results revealed that expressions of the tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6), activities of maleic dialdehyde (MDA) and myeloperoxidase (MPO), and cell apoptosis in LPS injection + CO inhalation group were (0.91+/-0.25) pg/mg protein, (0.64+/-0.05) pg/mg protein, (1.02+/-0.23) nmol/mg protein, (7.18+/-1.62) U/mg protein and (1.60+/-0.34)%, respectively, significantly lower than the corresponding values in LI group [(1.48+/-0.23) pg/mg protein, (1.16+/-0.26) pg/mg protein, (1.27+/-0.33) nmol/mg protein, (8.16+/-1.49) U/mg protein and (3.18+/-0.51) %, P<0.05]. Moreover, CO inhalation obviously increased the expressions of HO-1 and interlukin-10 (IL-10) and activity of superoxide dismutase (SOD) [(5.43+/-0.92), (0.26+/-0.07) pg/mg protein and (60.09+/-10.21) U/mg protein in LPS injection + CO inhalation group vs (3.08+/-0.82), (0.15+/-0.03) pg/mg protein and (50.98+/-6.88) U/mg protein in LI group, P<0.05]. LI was attenuated by CO inhalation. Our study demonstrates that inhalation of low concentration of CO protects lung against LPS-induced injury via anti-oxidant, anti-inflammation, anti-apoptosis and up-regulation of HO-1 expression.
Assuntos
Monóxido de Carbono/administração & dosagem , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Administração por Inalação , Animais , Apoptose/efeitos dos fármacos , Carboxihemoglobina/análise , Citocinas/biossíntese , Heme Oxigenase-1/genética , Pulmão/metabolismo , Pulmão/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/análise , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effects of carbon monoxide (CO) inhalation on the apoptosis of pulmonary cells in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS) and to investigate its mechanisms. METHODS: Eighteen male SD rats were randomly divided into three groups. The ALI group received LPS 5 mg/kg intravenously, while the control group received normal saline, and the CO inhalation group received an inhalation of 2.5 x 10(-4) CO (V/V) after ALI induced by LPS 5 mg/kg. The animals were sacrificed by exsanguinations and lung tissue was harvested at 3 h of observation for determination of the heme oxygenase-1 (HO-1) mRNA with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the level of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 with enzyme-linked immunosorbent assay (ELISA) and the maleic dialdehyde (MDA) concentration, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity with chemical methods. The extent of cell apoptosis was observed by using the flow cytometric method. RESULTS: The change of the levels of HO-1 mRNA, TNF-alpha, IL-6, IL-10, MDA, MPO, SOD and apoptotic cells of the ALI group was significant as compared with the control group [1.002 +/- 0.004, (0.47 +/- 0.06) pg/mg prot, (0.49 +/- 0.12) pg/mg prot, (0.42 +/- 0.08) pg/mg prot, (0.79 +/- 0.14) nmol/mg prot, (6.0 +/- 1.0) U/mg prot, (74 +/- 7) U/mg prot, (0.12 +/- 0.03)%, P < 0.05 or < 0.01], and lung injury was severe. The levels of TNF-alpha, IL-6, MDA, MPO, and apoptotic cells of the CO inhalation group [(0.91 +/- 0.25) pg/mg prot, (0.64 +/- 0.05) pg/mg prot, (1.02 +/- 0.23) nmol/mg prot, (7.2 +/- 1.6) U/mg prot, (1.60 +/- 0.34)%] were decreased, while HO-1, IL-10 and SOD expression [5.433 +/- 0.921, (0.26 +/- 0.07) pg/mg prot, (60 +/- 10) U/mg prot] were increased compared with the ALI group [(1.48 +/- 0.23) pg/mg prot, (1.16 +/- 0.26) pg/mg prot, (1.27 +/- 0.33) nmol/mg prot, (8.2 +/- 1.5) U/mg prot, (3.18 +/- 0.51)%, 3.081 +/- 0.823, (0.15 +/- 0.03) pg/mg prot, (51 +/- 7) U/mg prot, P < 0.05 or < 0.01], and lung injury was attenuated. CONCLUSION: CO inhalation protects lung from injury by regulating oxidative/anti-oxidative and inflammatory/anti-inflammatory disorders, inhibiting excessive cell apoptosis and up-regulating HO-1 expression, which may play an important role in the pathogenesis of LPS-induced ALI.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Apoptose/efeitos dos fármacos , Monóxido de Carbono/farmacologia , Heme Oxigenase-1/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Lipopolissacarídeos/efeitos adversos , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27µg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400µM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200µM. In addition, quercetin-PC at 200µM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200µM failed to do so. Molecular examinations revealed that quercetin-PC at 200µM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense.
Assuntos
Citoproteção/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeos/química , Quercetina/química , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Peróxido de Hidrogênio/farmacologia , Desintoxicação Metabólica Fase IIRESUMO
PURPOSE: There are six natural flavonoids studied recently and their effects on ocular blood flow measured with colored microsphere technique. It was found that three out of six compounds showed strong positive effects in increasing the ocular blood flow. In this study, we tried to find out whether these results can be translated on their effects to improve retinal function recovery after ischemic insult. METHODS: Electroretinography was used to measure the b-wave recovery as an indication of retinal function recovery. RESULTS: Naringenin, hesperetin, and rutin were found to produce marked positive effects on b-wave recovery, whereas naringin, hesperidin, and quercetin showed poor recovery of b-wave after ischemic insult of the retina. CONCLUSION: It was found that the compounds that showed strong increase of ocular blood flow also showed marked increase of retinal function recovery, whereas those that showed poor increase of ocular blood flow also showed poor effects on the retinal function recovery.
Assuntos
Artérias Ciliares/efeitos dos fármacos , Flavonoides/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Retina/efeitos dos fármacos , Artéria Retiniana/efeitos dos fármacos , Animais , Artérias Ciliares/fisiologia , Modelos Animais de Doenças , Feminino , Flavonoides/administração & dosagem , Ratos , Ratos Long-Evans , Fluxo Sanguíneo Regional/efeitos dos fármacos , Traumatismo por Reperfusão/fisiopatologia , Artéria Retiniana/fisiologia , Fatores de TempoRESUMO
PURPOSE: We have recently reported that the effect of a flavonoid on ocular blood flow depends upon the number of hydroxy (OH) groups in its backbone structure. To elucidate the structural features on the number and type of functional groups present in the flavonoid molecule plus the number of OH groups, flavonoids with four to five OH groups, with or without methoxy groups, were studied on their effects to affect the ocular blood flow and the retinal function recovery. METHODS: A colored microsphere technique was used to determine the ocular blood flow in albino rabbit eyes and electroretinography was used to measure the retinal function recovery. RESULTS: Flavonols with four free OH groups produced no effects on the ocular blood flow (fisetin, kaempferol), whereas flavanone and flavones with four free OH groups and without the C2-C3 double bond produced the rapid increment on ocular blood flow (dihydrofisetin and luteolin, respectively). Similarly, flavonols with five free OH groups produced no effects on the ocular blood flow (morin, quercetin). Yet, flavanone with five free OH groups and without the C2-C3 double bond produced the rapid increment on ocular blood flow (dihydroquercetin). Flavanols with five free OH groups and without the C2-C3 double bond and the carbonyl group produced no effects on the ocular blood flow (catechin). Flavonols with four free OH groups and a methoxy group on the 7 position produced no effects on the ocular blood flow (Rhamnetin). Flavonols with four free OH groups and a methoxy group at the 5 (5-methylquercetin) or 3' position (isorhamnetin) produced positive effects on the ocular blood flow also. Flavonol with five methoxy groups but no OH group produced positive effects on the ocular blood flow (pentamethylquercetin). Flavonols with an excessive number of OH groups, having both a catechol-like structure in the C ring and a catechol at the B ring, produced no effect on the ocular blood flow (rhamnetin, quercetin). Parallel results were obtained on retinal function recovery after ischemic insult. CONCLUSION: The presence of OH groups at certain positions and the double bond at C2-C3 in the flavonoid molecules, which produces lipophilic action, can affect the increment on ocular blood flow and retinal function recovery. O-methylation can increase ocular blood flow and retinal function recovery as well.
Assuntos
Olho/irrigação sanguínea , Flavonoides/química , Flavonoides/farmacologia , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/fisiopatologia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Olho/efeitos dos fármacos , Olho/fisiopatologia , Feminino , Flavonoides/administração & dosagem , Instilação de Medicamentos , Masculino , Microesferas , Coelhos , Ratos , Ratos Long-Evans , Fluxo Sanguíneo Regional/efeitos dos fármacos , Relação Estrutura-Atividade , Fatores de TempoRESUMO
PURPOSE: It has been found that the number of hydroxy groups in the molecule of flavones and flavanones affect the ocular blood flow significantly. However, the effects of dihydrogenation of flavones into flavanones on ocular blood flow and retinal function recovery have not been studied and required investigation. METHODS: The colored microsphere technique and electroretinography method were used for the study of ocular blood flow and retinal function, respectively. RESULTS: Maximum effects on ocular blood flow were obtained when there were 3 hydroxy groups in the molecule of flavones and flavanones. Dihydrogenation of flavones to flavanones increased the ocular blood flow further. The same is true for retinal function recovery after ischemic insult. CONCLUSION: These results indicate that hydrogenation is an excellent way to convert natural flavones into more potent compounds of flavanones.
Assuntos
Flavonas/administração & dosagem , Hidróxidos/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Retina/efeitos dos fármacos , Animais , Olho/irrigação sanguínea , Olho/efeitos dos fármacos , Feminino , Flavonas/química , Hidrogenação , Hidróxidos/química , Isquemia/tratamento farmacológico , Masculino , Hipertensão Ocular/tratamento farmacológico , Coelhos , Ratos , Ratos Long-Evans , Recuperação de Função Fisiológica/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Retina/fisiologiaRESUMO
PURPOSE: To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO). METHOD: Cell culture was used for in vitro experiments to determine the production of NO by NO donors and colored microsphere technique was used for in vivo experiments to determine the blood flow in various tissues of rabbit eyes. RESULTS: ZX-5 and ZX-4 are two geographic isomers with ZX-5 as trans-form and ZX-4 as cis-form. (1-phenyl-3-[3-methoxy-2-propoxy-5-[4-(3,4,5-trimethoxy-phenyl)-1,3-d lane-2-yl]phenyl]thiourea). It was found that ZX-5 released significant amount of NO at 3, 10, 30 microg/ml concentrations and increased choroid blood flow at 1%, 50 microl instillation into eyes. It was not effective on the blood flow of iris or ciliary body. The corresponding ZX-4 was not effective on ocular blood flow nor it released NO. CONCLUSION: ZX-5 can specifically increase the choroidal blood flow which could be useful to suppress the choroidal neovascularization in age-related macular degeneration (AMD). It is hoped that ZX-5 type of compounds could be used for the treatment/prevention of AMD in the elderly.
Assuntos
Corioide/efeitos dos fármacos , Óxido Nítrico/biossíntese , Tioureia/farmacologia , Animais , Células Cultivadas , Corioide/irrigação sanguínea , Corpo Ciliar/irrigação sanguínea , Técnicas In Vitro , Iris/irrigação sanguínea , Hipertensão Ocular/fisiopatologia , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Estereoisomerismo , Tioureia/análogos & derivados , Tioureia/químicaRESUMO
OBJECTIVE: To observe effects of norepinephrine (NE) on the therapeutic effects of nitric oxide (NO) inhalation in goats with endotoxin-induced acute respiratory distress syndrome (ARDS). METHODS: A model of septic ARDS was reproduced by an intravenous infusion of low dose endotoxin in six goats, and then these animals were treated with 40 x 10(-6) NO inhalation. After 30 minutes, intravenous infusion of NE in dose of 0.5 microg x kg(-1) x h(-1) was given. The dynamic changes in gas exchange and hemodynamics were measured with the aid of Swan-Ganz catheter and arterial blood gas analysis before and after the onset of ARDS, 30 minutes after NO inhalation and administration of NE. RESULTS: Inhalation of NO rapidly reduced mean pulmonary arterial pressure (MPAP), increased PaO(2), decreased alveolar-arterial partial pressure of oxygen difference (P (A-a) O(2)) and intrapulmonary shunt fraction (Qs/Qt) in septic ARDS goats. These changes were more pronounced when NE was given compared with NO inhalation alone. The combination of NO inhalation and NE infusion resulted in an increase in mean arterial pressure. CONCLUSION: Norepinephrine enhances the beneficial effect of nitric oxide inhalation on lung gas exchange in goats with endotoxin induced acute respiratory distress syndrome.
Assuntos
Óxido Nítrico/uso terapêutico , Norepinefrina/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Cabras , Hemodinâmica/efeitos dos fármacos , Troca Gasosa Pulmonar/efeitos dos fármacos , Síndrome do Desconforto Respiratório/fisiopatologiaRESUMO
OBJECTIVE: To observe the effect of combination of nitric oxide (NO) inhalation and inverse ratio ventilation (IRV) on oxygenation and hemodynamics in endotoxin-induced acute respiratory distress syndrome (ARDS) in sheep. METHODS: Sheep ARDS model was induced by an intravenous infusion of low dose endotoxin, and then animals were randomly divided into two groups. (1) NO group (n=6), inhalation of 40x10(-6) nitric oxide. (2) Combination group (n=6), receiving mechanical ventilation with IRV (inspiratory-to-expiratory ratio of 2:1) and inhalation of 40x10(-6) NO. The dynamic changes in gas exchange and hemodynamics were measured with the aid of Swan-Ganz catheter and arterial blood gas analysis before and after the onset of, ARDS and 30 minutes after treatment. RESULTS: The combination of IRV and 40x10(-6) NO inhalation rapidly reduced mean pulmonary arterial pressure (MPAP), increased PaO(2), decreased P((A-a))O(2), and Qs/Qt without inducing significant change in systemic hemodynamics, and it was a more effective method of correcting hypoxemia than inhalation of nitric oxide alone. NO inhalation did not change the airway pressure of the model, but the combined treatment resulted in reduction of peak inspiratory pressure and increase of mean airway pressure. CONCLUSION: The combined use of IRV and NO inhalation has an additive effect on improving oxygenation in endotoxin-induced acute respiratory distress syndrome in sheep.
Assuntos
Pneumopatias/terapia , Óxido Nítrico/uso terapêutico , Respiração com Pressão Positiva/métodos , Administração por Inalação , Animais , Gasometria , Terapia Combinada , Endotoxinas/administração & dosagem , Endotoxinas/toxicidade , Feminino , Pneumopatias/sangue , Pneumopatias/etiologia , Masculino , Óxido Nítrico/administração & dosagem , Troca Gasosa Pulmonar/efeitos dos fármacos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Ovinos , Resultado do TratamentoRESUMO
Choroidal neovascularization (CNV) is characterized by abnormal blood vessels growing from the choroid. Current remedies for CNV have not shown favorable therapeutic efficacy. It is urgent to identify and develop more safe and potent anti-CNV agents via multiple technologies. We previously showed that the natural product naringenin attenuated CNV. However, naringenin has poor water solubility and low bioavailability. Here, we prepared the ß-cyclodextrin (ß-CD) complex of naringenin and characterized it using infrared spectra and X-ray diffraction analyses. Determination of content and solubility in the complex showed that naringenin accounted for 20.53% in the complex and its solubility was increased by more than 10-fold. Using a laser-induced CNV model in rats we demonstrated that naringenin/ß-CD complex more significantly reduced CNV area than naringenin alone in rats. Furthermore, naringenin and its ß-CD complex significantly inhibited the mRNA and protein expression of VEGF, COX-2, PI3K, p38MAPK, MMP-2, and MMP-9 in retina and choroid tissues. Naringenin/ß-CD complex showed more significant inhibitory effect on VEGF and COX-2 expression than naringenin. These results collectively indicated that naringenin/ß-CD complex could be a promising therapeutic option for CNV and that the beneficial effects could be linked to the anti-inflammatory properties of naringenin.
Assuntos
Inibidores da Angiogênese , Corioide , Neovascularização de Coroide , Flavanonas , beta-Ciclodextrinas , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Corioide/irrigação sanguínea , Corioide/efeitos dos fármacos , Flavanonas/química , Flavanonas/farmacologia , Masculino , Metaloproteinases da Matriz/análise , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Espectrofotometria Infravermelho , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Difração de Raios X , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologiaRESUMO
AIM: To find the significant altered proteins in age-related macular degeneration (AMD) patients as potential biomarkers of AMD. METHODS: A comparative analysis of the protein pattern of AMD patients versus healthy controls was performed by means of proteomic analysis using two-dimensional gel electrophoresis followed by protein identification with MALDI TOF/TOF mass spectrometry. RESULTS: We identified 28 proteins that were significantly altered with clinical relevance in AMD patients. These proteins were involved in a wide range of biological functions including immune responses, growth cytokines, cell fate determination, wound healing, metabolism, and anti-oxidance. CONCLUSION: These results demonstrate the capacity of proteomic analysis of AMD patient plasma. In addition to the utility of this approach for biomarker discovery, identification of alterations in endogenous proteins in the plasma of AMD patient could improve our understanding of the disease pathogenesis.
RESUMO
We theoretically investigate the electronic transport between quantum Hall states and quantum anomalous Hall states in a zigzag edged graphene nanoribbon based two-terminal heterojunction. The electrical conductance of the system is calculated by the method of the non-equilibrium Green's function and Landauer-Büttiker formula. We find perfect transmission through the junction when the propagation direction of the charge carriers is the same at the same edge in both regions. However, when the propagation direction at the same edge is the opposite, the electrical conductance is smaller than the quantized value. In this case, snake states at the interface are responsible for the transmission. The results are explained with the aid of the local density of states near the interface. For higher magnetic field in the quantum Hall region or larger ribbon width, the edge states are better realized and quantized electrical conductance is strengthened. Finally, the effects of Anderson disorder and dephasing on the transmission are discussed.
Assuntos
Transporte de Elétrons , Grafite/química , Campos Magnéticos , Modelos Químicos , Modelos Moleculares , Nanotubos/química , Simulação por Computador , Nanotubos/ultraestrutura , Teoria QuânticaRESUMO
Treatment with inhaled carbon monoxide (CO) has been shown to ameliorate intestinal injury induced by lipopolysaccharide (LPS) or ischemia-reperfusion in experimental animals. We hypothesized that CO intraperitoneal administration (i.p) might provide similar protection against inhaled gas. In the present study, 1 h after intravenously receiving 5 mg/kg LPS, rats were exposed to either room air or 2 ml/kg of 250 ppm CO i.p for 1, 3, and 6 h. Intestinal tissues were collected to determine the levels of platelet activator factor (PAF), intercellular adhesion molecule-1 (ICAM-1), interleukin-10 (IL-10), maleic dialdehyde (MDA), cell apoptotic rate and the phosphorylated p38 mitogen activated protein kinase (MAPK), as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activity. After CO i.p, the increase of PAF, ICAM-1, MDA, MPO, and cell apoptosis rate induced by LPS was markedly reduced (P < 0.05 or 0.01), while the decrease of IL-10 and SOD was significantly increased (P < 0.05). Western blotting showed that the effects of CO i.p were mediated by p38 MAPK pathway. Thus, the results of our study show that CO i.p exerts potent protection against LPS induced injury to the intestine via anti-oxidant, anti-inflammation and anti-apoptosis, which may involve the p38 MAPK pathway.
Assuntos
Monóxido de Carbono/administração & dosagem , Monóxido de Carbono/farmacologia , Intestinos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Aldeídos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Injeções Intraperitoneais , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/citologia , Masculino , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Treatment with inhaled carbon monoxide (CO) has been shown to ameliorate intestinal injury in experimental animals induced by lipopolysaccharide (LPS) or ischemia-reperfusion. We hypothesized that CO intraperitoneal administration (i.p.) might provide similar protection to inhaled gas. This study aimed to investigate the effects of continuous 2 L/min of 250 ppm CO i.p. on rat intestine injury induced by LPS and to try to develop a more practical means of delivering the gas. METHODS: A total of 72 male Sprague-Dawley rats were randomly assigned to 4 groups: control group, CO i.p. group, LPS group and LPS+CO i.p. group. One hour after intravenously received 5 mg/kg LPS, the rats in LPS group and LPS+CO i.p. group were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively, and the rats of control group and CO i.p. group intravenously received an equal volume of 0.9% NaCl and 1 hour later, were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively. One, 3 and 6 hour of each group after treated with room air or CO i.p., the animals (n = 6 for each time point) were sacrificed and intestinal tissues were collected for determinating the levels of platelet activator factor (PAF) and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent assays. The maleic dialdehyde (MDA) content and the myeloperoxidase (MPO) activity were determined with a chemical method. The phosphorylated p38 mitogen activated protein kinase (MAPK) expression was assayed with Western blotting and the cell apoptotic rate with flow cytometery. The arterial oxygenation was measured by blood gas analysis, and the pathology determined by light microscope. RESULTS: After treatment with 2 L/min of 250 ppm CO i.p., the increase of PAF, ICAM-1, MDA, MPO, and cell apoptotic rate induced by LPS was markedly reduced (P < 0.05 or 0.01), and accompanied by ameliorating intestine injury. Western blotting showed that these effects of CO i.p. were mediated by p38 MAPK pathway. There were no significant differences in all observed parameters between control group and CO i.p. group. CONCLUSION: The injury to the intestine via anti-oxidant, anti-inflammation and anti-apoptosis, which may involve the p38 MAPK pathway, was induced by 2 L/min of 250 ppm CO i.p. exerting potent protection against LPS.
Assuntos
Monóxido de Carbono/farmacologia , Monóxido de Carbono/uso terapêutico , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Aldeídos/metabolismo , Animais , Western Blotting , Monóxido de Carbono/administração & dosagem , Citometria de Fluxo , Molécula 1 de Adesão Intercelular/metabolismo , Intestinos/patologia , Masculino , Microscopia , Peroxidase/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/tratamento farmacológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
AIM: To investigate the effects of low concentration carbon monoxide (CO) inhalation or intraperitoneal infusion on lipopolysaccharide (LPS) induced rat small intestine injury and to detect the roles of p38 mitogen-activated protein kinase (MAPK) pathway during CO administration. METHODS: SD rats with small intestine injury induced by 5 mg/kg LPS intravenous injection were challenged by room air, 2.5 x 10(-4)(V/V) CO inhalation or intraperitoneal infusion for 1 h, 3 h and 6 h differently. Then all animals were sacrificed, and the ileum tissues were homogenized for determination the levels of platelet activator factor(PAF) and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent assay, the pathology with light microscope, and the phosphorylated p38 MAPK expression with Western blot. RESULTS: Compared with either control, CO inhalation or intraperitoneal infusion group at the same time point, the levels of PAF, ICAM-1 and the phosphorylated p38 MAPK of LPS group were increased (all P < 0.01), but there were no statistics differences at the different time point of this group. PAF and ICAM-1 in both LPS injection + CO inhalation group and LPS injection + CO intraperitoneal infusion group were significantly lower than the corresponding value in LPS injection group at the same time point (all P < 0.05), while the expression of phosphorylated p38 MAPK was further up-regulated than that of LPS injection group (P < 0.05). However, there were no significant differences in these parameters between LPS injection+ CO inhalation group and LPS injection+ CO intraperitoneal infusion group. CONCLUSION: Low concentration CO inhalation and intraperitoneal infusion exerts the similar protection against LPS induced rat small intestine injury via down-regulating PAF and ICAM-1 expression. This may involve the p38 MAPK pathway.
Assuntos
Monóxido de Carbono/farmacologia , Intestino Delgado/patologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Regulação para Baixo , Inflamação/induzido quimicamente , Molécula 1 de Adesão Intercelular/metabolismo , Intestino Delgado/metabolismo , Masculino , Fosforilação , Fator de Ativação de Plaquetas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
On the basis of on-the-spot survey and analysis of water quality and bed mud in different cage culture section from April of 2002 to January of 2003, the analysis result indicate that the main influence of cage culture on environment are that: (1) It increase the content of nutrition salt, BOD, COD, organic matter and TSS, especially inorganic-nitrogen, inorganic-phosphor and ammonia nitrogen; (2) It enrich N, P, sulphide and organic matter in sediment. The most obvious is nitrogen, sulphide and ammonia nitrogen, next is total nitrogen and organic matter.