乙醛脱氢酶2和线粒体渗透转换参与乙醇后处理的心肌保护作用  

Activation of mitochondrial aldehyde dehydrogenase 2 and inhibition of mitochondrial permeability transition pore involved in cardioprotection of ethanol postconditioning

作　　者：李正红[1] 姜翠荣[1] 夏满莉[2] 叶红伟[1] 关宿东[1] 高琴[1] 

机构地区：[1]蚌埠医学院生理学教研室,安徽蚌埠233030 [2]嘉兴学院医学院生理学教研室,浙江嘉兴314001

出　　处：《浙江大学学报（医学版）》2010年第6期566-571,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：安徽省自然科学基金资助项目(090413097);嘉兴市科技局资助项目(2010AY1061)

摘　　要：目的:探讨乙醇后处理心肌保护作用是否与促进线粒体乙醛脱氢酶2(aldehydedehydrogenase 2,ALDH2)的生成和抑制线粒体渗透性转换孔道的开放有关。方法:采用离体大鼠心脏Langendorff灌流方法,局部结扎冠状动脉左前降支30 min,复灌120 min复制心肌缺血/复灌模型。测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶(lactate dehydrogenase,LDH)含量。TTC染色法测定心肌梗死面积。RT-PCR测定左心室前壁心尖组织线粒体ALDH2 mRNA的表达。结果:与单纯缺血/复灌相比,乙醇后处理明显促进了左室发展压、左心室内压最大上升和下降速率的恢复,降低复灌期冠脉流出液中LDH的释放和心肌梗死面积,ALDH2 mRNA表达增高。线粒体渗透性转换孔道开放剂苍术苷减弱了乙醇后处理的作用,抑制了心室动力学指标的恢复,LDH释放增多,梗死面积增加,同时ALDH2 mRNA表达降低。结论:乙醇后处理心肌保护作用可能与促进线粒体乙醛脱氢酶2的生成和抑制线粒体渗透性转换孔道的开放有关。Objective: To investigate whether activation of mitochondrial aldehyde dehydrogenase 2(ALDH2) and inhibition of mitochondrial permeability transition pore(mitoPTP) were involved in the cardioprotection of ethanol postconditioning in isolated rat heart.Methods: Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 min of regional ischemia(occlusion of left anterior descending artery) followed by 120 min of reperfusion.The ventricular hemodynamic parameters and lactate dehydrogenase(LDH) release during reperfusion were measured.Infarct size was measured by TTC staining method and the expression of ALDH2 at mRNA level of left anterior myocardium was detected by RT-PCR.Results: In contrast to ischemia and reperfusion,ethanol postconditioning improved the recovery of left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure during reperfusion,reduced LDH release and infarct size.The expression of ALDH2 mRNA level was increased.Administration of mitoPTP activator atractyloside attenuated the effect of ethanol postconditioning,LDH release and infarct size were increased,and the recovery of hemodynamic parameters was inhibited.The expression of ALDH2 mRNA was decreased.Conclusion: Ethanol postconditioning has cardioprotection effect,which may be associated with upregulating mitochondrial ALDH2 mRNA expression and inhibiting the opening of mitochondrial permeability transition pore.

关 键 词：线粒体 心脏 心肌再灌注损伤/病理生理学 心肌缺血/病理生理学 乙醇 醛脱氢酶 乙醇后处理 心脏 缺血/复灌损伤 线粒体乙醛脱氢酶2 线粒体渗透性转换孔 

分 类 号：R363.2[医药卫生—病理学]