线粒体通透性转换孔在远距预处理心肌保护中的作用

Role of Mitochondrial Permeability Transition Pore in Cardioprotection by Remote Preconditioning

目的：观察线粒体通透性转换孔在远距预处理心肌保护中的作用。方法：夹闭麻醉的雄性SD大鼠右下肢股动脉5min,松开复灌5min,共3个循环,造成大鼠肢体远距预处理模型（RPC）。结扎冠状动脉前降支缺血30min后松开复灌120min,造成心肌缺血/复灌（I/R）损伤;用TTC染色法测量心肌梗死面积。检测血浆中乳酸脱氢酶（LDH）活性和线粒体通透性转换孔开（MPTP）放。结果：RPC减小了I/R引起的心肌梗死面积,减少了复灌时血浆LDH水平。MPTP开放剂苍术苷（Atr,5mg/kg）减弱了RPC的作用。而MPTP抑制剂环孢菌素A（CsA,10mg/kg）减轻了I/R的作用。在离体心肌细胞上,RPC减小了MPTP的开放程度;MPTP开放剂Atr（20mmol/L）取消了RPC的作用。结论：远距预处理的心肌保护作用可能涉及线粒体通透性转换孔开放的抑制。

Objective： To investigate the role of mitochondrial permeability transition pore （MPTP） in the cardioprotection by remote preconditioning （ RPC）. Methods： RPC was induced in anesthetized male Sprague - Dawley rats by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. Myocardial ischemia/reperfusion（I/R） injury was achieved by ligation of the left anterior descending coronary artery for 30 min and then reperfusion for 120 min. Infarct size was determined by 2,3,5 - triphenyhetrazolium chloride （TTC） staining method. The level of lactate dehydragenase （LDH） in plasma and the opening of the mitochondrial permeability transition pore （MPTP） was measured. Results： RPC significantly decreased the infarct size and plasma lactate de- hydrogenase level induced by I/R, and these effects were attenuated by atractyloside（Atr, 5 mg/kg） , a MPTP activator. However, administration of cyclosporin A （ CsA, 10 mg/kg） , an inhibitor of MPTP, decreased the effect of I/R. In isolated ventricular myocytes loaded with calcein, RPC decreased the MPTP opening, and this effect was attenuated by Atr （20 mmol/L）. Conclusions： Inhibition of MPTP opening is involved in the cardioprotection by RPC.