乙醇后处理心肌保护作用的抗氧化机制探讨

    The anti-oxidative mechanism in the cardioprotection of ethanol postconditioning

    • 摘要: 目的:探讨乙醇后处理(EtOH)的心肌保护作用与抗氧化应激损伤关系。方法:采用离体大鼠心脏Langendorff灌流法,局部结扎冠状动脉左前降支30 min,复灌120 min复制心肌缺血-再灌注损伤(I/R)模型。测定心室动力学指标及心肌组织超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量,RT-PCR检测线粒体乙醛脱氢酶2(ALDH2)、Bax、Bcl-2 mRNA表达。结果:与I/R组相比,EtOH明显促进左心室发展压、左心室内压最大上升和下降速率的恢复,心肌组织中SOD活力增加,MDA含量降低,Bcl-2表达增加,Bax表达降低(P<0.01)。ALDH2阻断剂氨基氰减弱了EtOH的作用,抑制了心室动力学指标的恢复,心肌组织中SOD活力降低,MDA含量增加,Bcl-2表达降低,Bax表达增加(P<0.01)。结论:EtOH的心肌保护作用可能与激动ALDH2、降低I/R引起的氧化应激损伤和减少心肌细胞凋亡有关。

       

      Abstract: Objective:To investigate the protective effects of ethanol postconditioning on isolated rats' hearts, and discuss the antioxidative mechanism. Methods:Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 minutes of regional ischemia(occlusion of left anterior descending artery) followed by 120 minutes of reperfusion. The ventricular hemodynamic parameters were measured. SOD activity and MDA content were detected to evaluate cell antioxidant ability. The expressions of aldehyde dehydrogenase 2,Bcl-2 and Bax at mRNA level of left anterior myocardium were detected by RT-PCR analysis. Results:Compared with ischemia-reperfusion group, ethanol postconditioning improved the recovery of left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure(P<0.01),SOD activity was increased and the content of MDA was decreased,Bcl-2 mRNA expression was increased,while Bax mRNA expression was decreased. Administration of ALDH2 inhibitor CYA attenuated the effect of ethanol postconditioning,the recovery of hemodynamic parameters were inhibited(P<0.01),SOD activity was decreased and the content of MDA was increased,Bcl-2 mRNA expression was decreased,Bax mRNA expression was increased. Conclusions:The protective effect of ethanol postconditioning on isolated rats' hearts is related to upregulating mitochondrial ALDH2 mRNA expression,likely through its antioxidative role and reduction of myocardial apoptosis.

       

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