Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postcon...Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 μmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 μmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevofluran展开更多
Objective： To explore the effects and molecular mechanisms of the combination between total Astragalus extract （TAE） and total Panax notoginseng saponins （TPNS） against cerebral ischemia- reperfusion injury. Meth...Objective： To explore the effects and molecular mechanisms of the combination between total Astragalus extract （TAE） and total Panax notoginseng saponins （TPNS） against cerebral ischemia- reperfusion injury. Methods： C57BL/6 mice were randomly divided into sham-operated group, model group, TAE （110 mg/kg） group, TPNS （115 mg/kg） group, TAE-TPNS combination group and Edaravone （4 mg/kg） group, treated for 4 days, then, cerebral ischemia-repeffusion injury was established by bilateral common carotid artery （CCA） ligation for 20 min followed by reperfusion for 1 and 24 h. Results： TPNS could increase adenosine triphosphate （ATP） level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate （ADP） contents and Na＋-K＋-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinasel/2 （p-JNK1/2）, cytochrome C （Cyt C）, cysteine aspartic acid-specific protease （Caspase）-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone. Conclusion： The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.展开更多
Background Studies suggested that anesthetics administered upon the early reperfusion or ＂anesthetic postconditioning＂ could protect post-ischemic hearts against myocardial ischemia reperfusion injury （MIRI）. Howe...Background Studies suggested that anesthetics administered upon the early reperfusion or ＂anesthetic postconditioning＂ could protect post-ischemic hearts against myocardial ischemia reperfusion injury （MIRI）. However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning （SpostC） in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase （PI3K）, extracellular signal-regulated kinase 1 and 2 （ERK 1/2）, mitochondrial KATP channels （mitOKAme） and mitochondrial permeability transition pore （mPTP）, by selectively inhibiting PI3K, ERK 1/2, mitOKATP, with LY294002 （LY）, PD98059 （PD）, 5-hydroxydecanoate （5-HD） and by directly opening of mPTP with atractyloside （ATR）, respectively. Methods Isolated rat hearts were randomly assigned to one of the 12 groups （n=-15）： Time control （continuous perfusion）, ISCH （30 minutes of ischemia followed by 60 minutes of reperfusion alone）, SpostC （3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia）, ISCH＋LY, ISCH＋PD, ISCH＋ATR, ISCH＋5-HD and ISCH＋ dimethyl sulfoxide （DMSO） groups （LY, PD, ATR, 5-HD and DMSO （the vehicle） was administered respectively during the first 15 minutes of reperfusion following test ischemia）, SpostC＋LY, SpostC＋PD, SpostC＋ATR and SpostC＋5-HD groups （LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively）. Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride （TTC） staining. Lactate dehydrogenase （LDH）, creatine kinase-MB （CK-MB） and cardiac troponin I （cTnl） released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD＋ content in myocardium, a marker of mPTP o展开更多
Objective: To explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injur...Objective: To explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injury. Methods: Hippocampal neurons were obtained from rat embryo and were cultured in vitro. The ischemia and reperfusion of cultured rat hippocampal neurons were simulated by oxygen-glucose deprivation (OGD) and recovery. OGD at different time points ((0.25) h to (3.0) h) and then the same recovery (24 h) were prepared. Annexin (V-PI) staining and flow cytometry examined neuron death and apoptosis at different time after injury. Results: After OGD and recovery, both necrosis and apoptosis were observed. At different times after OGD, there were statistically significant differences in neuron necrosis rate (P<(0.05)), but not in apoptosis rate (P>(0.05)). At recovery, survival rate of hippocampal neurons further decreased while apoptosis rate increased. Furthermore, apoptosis rates of different time differed greatly (P<(0.05)). Apoptosis rate gradually increased with significant difference among those of different time points (P<(0.05)). However, 2 h after ischemia, apoptosis rate decreased markedly. Conclusions: Apoptosis is an important pathway of delayed neuron death. The therapeutic time window should be within 2 h after cerebral ischemia and hypoxia.展开更多
AIM： To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion （I/R） injury are associated with increasing heat shock protein 70 （Hsp70） expression and antioxidant...AIM： To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion （I/R） injury are associated with increasing heat shock protein 70 （Hsp70） expression and antioxidant enzyme activity. METHODS： Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C ＋ I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin （50 mg/kg） was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C ＋ I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, liver tissue NO2- ＋ NO3-, malondialdehyde （MDA） content, superoxide dismutase （SOD）, catalase （CAT）, nitricoxide synthase （NOS） and myeloperoxidase （MPO） activity, HspT0 expression and apoptosis ratio. RESULTS： Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusioninduced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C ＋ I/R group, and a significant increase of MDA, NO2^- ＋ NO3^- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C ＋ I/R group. Curcumin also decreased the activity of inducible NO synthase （iNOS） in liver after reperfusion,but had no effect on the level of endothelial NO synthase （eNOS） after reperfusion in liver. The 7 d survival rate was significantly higher in C ＋ I/R group than in I/R group. CONCLUSION： Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.展开更多
基金Project supported by the National Natural Science Foundation ofChina (No. 30772090)the Natural Science Foundation of ZhejiangProvince (No. Y204141)+2 种基金the Foundation from Science and Technology Department of Zhejiang Province (No. 2007R10034)theFoundation from Personnel Department of Zhejiang Province (NoJ20050046)the Foundation from Health Department of ZhejiangProvince (No. 2007QN007), China
文摘Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 μmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 μmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevofluran
基金Supported by National Natural Science Foundation of China(No.81102557)Doctoral Program Foundation of Higher Education of China(No.20104323110001)+4 种基金Key Project of Hunan Province Education Department(No.08A050)Aid Project for Innovation Platform Open Fund of Hunan Province University(No.11K050 and No.14K068)Key Project of Administration of Traditional Chinese Medicine of Hunan Province(No.201301)General Project of Science and Technology Department of Hunan Province(No.2014SK3001)General Project of Education Bureau of Hunan Province(No.11C0963)
文摘Objective： To explore the effects and molecular mechanisms of the combination between total Astragalus extract （TAE） and total Panax notoginseng saponins （TPNS） against cerebral ischemia- reperfusion injury. Methods： C57BL/6 mice were randomly divided into sham-operated group, model group, TAE （110 mg/kg） group, TPNS （115 mg/kg） group, TAE-TPNS combination group and Edaravone （4 mg/kg） group, treated for 4 days, then, cerebral ischemia-repeffusion injury was established by bilateral common carotid artery （CCA） ligation for 20 min followed by reperfusion for 1 and 24 h. Results： TPNS could increase adenosine triphosphate （ATP） level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate （ADP） contents and Na＋-K＋-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinasel/2 （p-JNK1/2）, cytochrome C （Cyt C）, cysteine aspartic acid-specific protease （Caspase）-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone. Conclusion： The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.
文摘Background Studies suggested that anesthetics administered upon the early reperfusion or ＂anesthetic postconditioning＂ could protect post-ischemic hearts against myocardial ischemia reperfusion injury （MIRI）. However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning （SpostC） in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase （PI3K）, extracellular signal-regulated kinase 1 and 2 （ERK 1/2）, mitochondrial KATP channels （mitOKAme） and mitochondrial permeability transition pore （mPTP）, by selectively inhibiting PI3K, ERK 1/2, mitOKATP, with LY294002 （LY）, PD98059 （PD）, 5-hydroxydecanoate （5-HD） and by directly opening of mPTP with atractyloside （ATR）, respectively. Methods Isolated rat hearts were randomly assigned to one of the 12 groups （n=-15）： Time control （continuous perfusion）, ISCH （30 minutes of ischemia followed by 60 minutes of reperfusion alone）, SpostC （3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia）, ISCH＋LY, ISCH＋PD, ISCH＋ATR, ISCH＋5-HD and ISCH＋ dimethyl sulfoxide （DMSO） groups （LY, PD, ATR, 5-HD and DMSO （the vehicle） was administered respectively during the first 15 minutes of reperfusion following test ischemia）, SpostC＋LY, SpostC＋PD, SpostC＋ATR and SpostC＋5-HD groups （LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively）. Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride （TTC） staining. Lactate dehydrogenase （LDH）, creatine kinase-MB （CK-MB） and cardiac troponin I （cTnl） released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD＋ content in myocardium, a marker of mPTP o
文摘Objective: To explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injury. Methods: Hippocampal neurons were obtained from rat embryo and were cultured in vitro. The ischemia and reperfusion of cultured rat hippocampal neurons were simulated by oxygen-glucose deprivation (OGD) and recovery. OGD at different time points ((0.25) h to (3.0) h) and then the same recovery (24 h) were prepared. Annexin (V-PI) staining and flow cytometry examined neuron death and apoptosis at different time after injury. Results: After OGD and recovery, both necrosis and apoptosis were observed. At different times after OGD, there were statistically significant differences in neuron necrosis rate (P<(0.05)), but not in apoptosis rate (P>(0.05)). At recovery, survival rate of hippocampal neurons further decreased while apoptosis rate increased. Furthermore, apoptosis rates of different time differed greatly (P<(0.05)). Apoptosis rate gradually increased with significant difference among those of different time points (P<(0.05)). However, 2 h after ischemia, apoptosis rate decreased markedly. Conclusions: Apoptosis is an important pathway of delayed neuron death. The therapeutic time window should be within 2 h after cerebral ischemia and hypoxia.
文摘AIM： To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion （I/R） injury are associated with increasing heat shock protein 70 （Hsp70） expression and antioxidant enzyme activity. METHODS： Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C ＋ I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin （50 mg/kg） was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C ＋ I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, liver tissue NO2- ＋ NO3-, malondialdehyde （MDA） content, superoxide dismutase （SOD）, catalase （CAT）, nitricoxide synthase （NOS） and myeloperoxidase （MPO） activity, HspT0 expression and apoptosis ratio. RESULTS： Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusioninduced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C ＋ I/R group, and a significant increase of MDA, NO2^- ＋ NO3^- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C ＋ I/R group. Curcumin also decreased the activity of inducible NO synthase （iNOS） in liver after reperfusion,but had no effect on the level of endothelial NO synthase （eNOS） after reperfusion in liver. The 7 d survival rate was significantly higher in C ＋ I/R group than in I/R group. CONCLUSION： Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.
