目的:研究茜草素对Wistar大鼠肾叶间动脉及其平滑肌细胞大电导钙激活钾通道(Large Conductance Calcium Activated Potassium Channels;BKCa)的影响。方法:压力型小动脉测量仪用于观察给予茜草素前后肾叶间动脉血管直径的变化;全细胞膜...目的:研究茜草素对Wistar大鼠肾叶间动脉及其平滑肌细胞大电导钙激活钾通道(Large Conductance Calcium Activated Potassium Channels;BKCa)的影响。方法:压力型小动脉测量仪用于观察给予茜草素前后肾叶间动脉血管直径的变化;全细胞膜片钳技术用于研究茜草素对离体的Wistar大鼠肾叶间动脉平滑肌细胞BKCa介导的外向电流的调节作用。结果:(1)茜草素(10^(-7)~3×10^(-5)mol/L)舒张肾叶间动脉(P<0.01);(2)茜草素(10^(-7)~3×10^(-5)mol/L)增强Wistar大鼠肾叶间动脉平滑肌细胞外向电流(60 m V)呈浓度依赖性(P<0.05);(3)在0 m V^60 m V,茜草素(10-5mol/L)增强Wistar大鼠肾叶间动脉平滑肌细胞外向电流呈电压依赖性(P<0.05);(4)TEA(10-4mol/L)阻断茜草素(10-5mol/L)增强的肾叶间动脉平滑肌细胞外向电流(60 m V)(P<0.01);(5)10^(-7)mol/L的BKCa阻断剂伊比利亚毒素(ib TX)阻断茜草素(10^(-5)mol/L)对肾叶间动脉平滑肌细胞外向电流(60 m V)的增强作用(P<0.01)。结论:茜草素通过激活更多BKCa开放促进钾离子外流,引起Wistar大鼠肾叶间动脉平滑肌细胞超极化,舒张肾叶间动脉血管。展开更多
OBJCETIVE Epidemiologic studies have demonstrated that consumption of moderate amounts of red wine is associated with significant reductions in incidences of cardiovascular and cerebrovascular diseases,which may be re...OBJCETIVE Epidemiologic studies have demonstrated that consumption of moderate amounts of red wine is associated with significant reductions in incidences of cardiovascular and cerebrovascular diseases,which may be related to alcohol in red wine.Our previous study demonstrated that ethanol ingestion 24 h prior to induction of cerebral ischemic/reperfusion(I/R)reduced delayed neuronal death(DND).Our most recent results supported a role for big Ca2+-sensitive K+channel(BKCa channel)activation in the neuroprotective effects of ethanol preconditioning(Et OH-PC)in global cerebral I/R.Therefore,we hypothesis that moderate Et OH-PC activates BKCa channel to protect brain damage induced by focal cerebral I/R.This project will utilize focal cerebral I/R animal model to explore the function of BKCa channel in Et OH-PC protection in vivo levels by means of pharmacological intervention such as BKCa channel opene(rNS11021,NS)and blocke(rpaxilline,PX).The results will provide theoretical evidence for neuroprotective effect of moderate alcohol preconditioning against ischemic stroke,and the conclusion will also bring to a concept that extrinsic moderate ethanol preconditioning may activate intrinsic protective mechanism in the brain.METHODS The SD rat were randomly divided into the following six groups(n=10):sham,I/R,Et OH-PC+I/R,NS11021-PC+I/R,paxilline+Et OH-PC+I/R,Paxilline+NS11021-PC+I/R.Both Et OH-PC and NS11021-PC(0.1mg·kg-1;ip)were induced 24 h before I/R.The volume of 95%ethanol to be instilled(inμL)was calculated as follows:〔body weight(g)×0.6〕+0.3.This volume of ethanol was mixed in 0.3 m L of sterile distilled water just before administration to the animals by gavage.The Paxilline(2.5 mg·kg-1;ip)was administered 10min beforeEt OH-PC and NS11021-PC.The right middle cerebral artery occlusion(MCAO)was produced by inversion of a 4-0-nylon filament.The filament was withdrawn 2 h after onset of MCAO and then reperfused.Neurological deficits and infarct volume were measured 24 h after I/R.Another 36 rats were randomly divided into 6 groups as above,6 in each group.DWI were performed 2h after ischemic and T2WI MRI were performed 24 h after I/R to observe the infarct volume of brain and the penumbra volume of brain in each group.Then rats were killed and detected the apoptotic cell death and degeneration of neurons.RESULTS Compared to I/R group,the neurological score(P<0.01),the infarct volume of brain(P<0.01),the infarct volume of ischemic penumbra(P<0.01),the percentage of apoptotic cell death(P<0.01)and the percentage of degenerative neurons(P<0.01)were significantly decreased after ethanol preconditioning,while these changes were reversed by paxilline(P<0.05);compared to I/R group,the neurological score(P<0.01),the infarct volume of brain(P<0.01),the infarct volume of ischemic penumbra(P<0.01),the percentage of apoptotic cell death(P<0.01)and the percentage of degenerative neurons(P<0.01)were significantly decreased after NS11021 preconditioning,while these changes were reversed by paxilline(P<0.05).CONCLUSION Our results show that moderate alcohol preconditioning activates BKCa channels to protect brain damage induced by focal cerebral I/R.展开更多
文摘目的:研究茜草素对Wistar大鼠肾叶间动脉及其平滑肌细胞大电导钙激活钾通道(Large Conductance Calcium Activated Potassium Channels;BKCa)的影响。方法:压力型小动脉测量仪用于观察给予茜草素前后肾叶间动脉血管直径的变化;全细胞膜片钳技术用于研究茜草素对离体的Wistar大鼠肾叶间动脉平滑肌细胞BKCa介导的外向电流的调节作用。结果:(1)茜草素(10^(-7)~3×10^(-5)mol/L)舒张肾叶间动脉(P<0.01);(2)茜草素(10^(-7)~3×10^(-5)mol/L)增强Wistar大鼠肾叶间动脉平滑肌细胞外向电流(60 m V)呈浓度依赖性(P<0.05);(3)在0 m V^60 m V,茜草素(10-5mol/L)增强Wistar大鼠肾叶间动脉平滑肌细胞外向电流呈电压依赖性(P<0.05);(4)TEA(10-4mol/L)阻断茜草素(10-5mol/L)增强的肾叶间动脉平滑肌细胞外向电流(60 m V)(P<0.01);(5)10^(-7)mol/L的BKCa阻断剂伊比利亚毒素(ib TX)阻断茜草素(10^(-5)mol/L)对肾叶间动脉平滑肌细胞外向电流(60 m V)的增强作用(P<0.01)。结论:茜草素通过激活更多BKCa开放促进钾离子外流,引起Wistar大鼠肾叶间动脉平滑肌细胞超极化,舒张肾叶间动脉血管。
文摘血管平滑肌（VSM）细胞和内皮细胞（EC）都表达K^＋通道，微血管平滑肌细胞至少表达4种不同类别的K^＋通道，内向整流性钾通道[inward rectifier K^＋（KIR）channel]；ATP敏感性钾通道[（ATP—sensitive K^＋（KATP）channel]；电压门控式钾通道[vohage—gated K^＋（Kv）channel]；大电导钙激活钾通道[the large conductance，Ca^2＋-activated K K^＋（MaxiK，BKCa）channel]。
基金The project supported by NSFC(81171079,81271312)
文摘OBJCETIVE Epidemiologic studies have demonstrated that consumption of moderate amounts of red wine is associated with significant reductions in incidences of cardiovascular and cerebrovascular diseases,which may be related to alcohol in red wine.Our previous study demonstrated that ethanol ingestion 24 h prior to induction of cerebral ischemic/reperfusion(I/R)reduced delayed neuronal death(DND).Our most recent results supported a role for big Ca2+-sensitive K+channel(BKCa channel)activation in the neuroprotective effects of ethanol preconditioning(Et OH-PC)in global cerebral I/R.Therefore,we hypothesis that moderate Et OH-PC activates BKCa channel to protect brain damage induced by focal cerebral I/R.This project will utilize focal cerebral I/R animal model to explore the function of BKCa channel in Et OH-PC protection in vivo levels by means of pharmacological intervention such as BKCa channel opene(rNS11021,NS)and blocke(rpaxilline,PX).The results will provide theoretical evidence for neuroprotective effect of moderate alcohol preconditioning against ischemic stroke,and the conclusion will also bring to a concept that extrinsic moderate ethanol preconditioning may activate intrinsic protective mechanism in the brain.METHODS The SD rat were randomly divided into the following six groups(n=10):sham,I/R,Et OH-PC+I/R,NS11021-PC+I/R,paxilline+Et OH-PC+I/R,Paxilline+NS11021-PC+I/R.Both Et OH-PC and NS11021-PC(0.1mg·kg-1;ip)were induced 24 h before I/R.The volume of 95%ethanol to be instilled(inμL)was calculated as follows:〔body weight(g)×0.6〕+0.3.This volume of ethanol was mixed in 0.3 m L of sterile distilled water just before administration to the animals by gavage.The Paxilline(2.5 mg·kg-1;ip)was administered 10min beforeEt OH-PC and NS11021-PC.The right middle cerebral artery occlusion(MCAO)was produced by inversion of a 4-0-nylon filament.The filament was withdrawn 2 h after onset of MCAO and then reperfused.Neurological deficits and infarct volume were measured 24 h after I/R.Another 36 rats were randomly divided into 6 groups as above,6 in each group.DWI were performed 2h after ischemic and T2WI MRI were performed 24 h after I/R to observe the infarct volume of brain and the penumbra volume of brain in each group.Then rats were killed and detected the apoptotic cell death and degeneration of neurons.RESULTS Compared to I/R group,the neurological score(P<0.01),the infarct volume of brain(P<0.01),the infarct volume of ischemic penumbra(P<0.01),the percentage of apoptotic cell death(P<0.01)and the percentage of degenerative neurons(P<0.01)were significantly decreased after ethanol preconditioning,while these changes were reversed by paxilline(P<0.05);compared to I/R group,the neurological score(P<0.01),the infarct volume of brain(P<0.01),the infarct volume of ischemic penumbra(P<0.01),the percentage of apoptotic cell death(P<0.01)and the percentage of degenerative neurons(P<0.01)were significantly decreased after NS11021 preconditioning,while these changes were reversed by paxilline(P<0.05).CONCLUSION Our results show that moderate alcohol preconditioning activates BKCa channels to protect brain damage induced by focal cerebral I/R.
