线粒体通透性转换孔在远程预处理心脏保护中的作用

[Role of mitochondrial permeability transition pore in cardioprotection by remote preconditioning].

作者信息

Cao Yang, Zhang Shi-Zhong, Xia Qiang

机构信息

Medical Science College of China Three Gorges University, Yichang 443002, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009 Nov;25(4):516-20.

PMID:21158047

Abstract

AIM

To investigate the role of mitochondrial permeability transition pore (MPTP) in the cardioprotection by remote preconditioning (RPC).

METHODS

Remote Precondition (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-triphenyltetrazolium chloride (TTC) staining method. The level of lactate dehydragenase (LDH) in plasma and the opening of the mitochondrial permeability transition pore (MPTP) were measured.

RESULTS

RPC significantly decreased the infarct size and plasma lactate dehydrogenase 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 micromol/L).

CONCLUSION

Inhibition of MPTP opening is involved in the cardioprotection by RPC.

摘要

目的

探讨线粒体通透性转换孔（MPTP）在远程预处理（RPC）心脏保护作用中的作用。

方法

在麻醉的雄性Sprague-Dawley大鼠中诱导远程预处理（RPC），通过对右股动脉进行3个循环的5分钟阻断，随后5分钟再灌注。通过结扎左冠状动脉前降支30分钟，然后再灌注120分钟来实现心肌缺血/再灌注（I/R）损伤。通过2,3,5-三苯基氯化四氮唑（TTC）染色法测定梗死面积。检测血浆中乳酸脱氢酶（LDH）水平以及线粒体通透性转换孔（MPTP）的开放情况。

结果

RPC显著减小了I/R诱导的梗死面积和血浆乳酸脱氢酶水平，而这些作用被MPTP激活剂苍术苷（Atr，5mg/kg）减弱。然而，给予MPTP抑制剂环孢素A（CsA，10mg/kg）可减轻I/R的作用。在装载有钙黄绿素的分离心室肌细胞中，RPC减少了MPTP的开放，而这种作用被Atr（20μmol/L）减弱。