线粒体乙醛脱氢酶2在心肌缺血后处理中的作用

Role of mitochondrial aldehyde dehydrogenase 2 in postconditioning induced cardioprotection

目的探讨线粒体乙醛脱氢酶2(aldehyde dehydrogen-ase 2,ALDH2)在离体大鼠心肌缺血后处理中的保护作用。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30min,复灌120min模拟心肌缺血/复灌模型。缺血后处理采用复灌初期立即给予反复6次的10s复灌/10s全心缺血的循环。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。实验结束后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、Bcl-2和Bax mR-NA的表达。结果与单纯缺血/复灌组相比,缺血后处理明显促进左室发展压、左室做功的恢复,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,Bcl-2/Bax mRNA比值增高。ALDH2阻断剂氨基氰减弱了缺血后处理的作用。结论缺血后处理部分通过增强线粒体乙醛脱氢酶2的表达发挥心肌保护作用。

Aim To investigate the role of mitochondrial aldehyde dehydrogenase 2 （ ALDH2） in the cardio-protection of ischemic postconditioning in isolated rat hearts. 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 reperfusion. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion. The ventricular hemodynamic parameters and lactate dehydrogenase （ LDH） release during reperfusion were measured. The infarct size was measured by TTC staining method. The expressions of ALDH2,Bcl-2 and Bax at mRNA level of left anterior myocardium were detected by RT-PCR analysis. Results In contrast to ischemia and reperfusion,ischemic postconditioning improved the recovery of left ventricular developed pressure,rate pressure product during reperfusion,and reduced LDH release and infarct size. The expressions of ALDH2 mRNA level and the ratio of Bcl-2 /Bax were increased. Adminis-tration of ALDH2 antagonist cyanamide at the beginning of reperfusion attentuated the role of ischemic postconditioning. Conclusion Ischemic postconditioning plays a role in the cardioprotection partially through increasing mitochondrial ALDH2 mRNA expression.