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心肌再灌注损伤保护的机制和策略

习瑾昆, 金元哲, 崔勋, 徐哲龙

北卡罗来纳大学教堂山分校麻醉系.北卡罗来纳州 27599

摘要

局部缺血部位快速再灌注虽然保护了心肌,但也引起再灌注损伤。目前还没有减轻再灌注损伤的特效疗法,但近年来研究显示,G蛋白耦联受体(G protein--coupled receptor, GPCR)的激动剂、胰岛素和缺血后处理可以在各种实验条件和各类动物模型中有效抵抗再灌注损伤。这些干预手段启动的心脏保护机制可能包括激活再灌注损伤补救激酶(reperfusion injurysalvage kinase, RISK)途径、抑制糖原合酶激酶--3#beta#(glycogen synthase kinase 3#beta#, GSK--3#beta#)以及抑制线粒体膜通透性转换孔(mitochondrial permeability transition pore, mPTP)开放等。这些研究成果有利于开发治疗急性心肌梗死的有效临床手段。

关键词： 再灌注损伤; 心脏保护; G蛋白耦联受体; 胰岛素; 缺血后处理; 线粒体膜通透性转换孔

Cardioprotection against reperfusion injury: updated mechanisms and strategies

Xi Jinkun, Jin Yuanzhe, Cui Xun, Xu Zhelong

Department of Anesthesiology, the University of North Carolina at Chapel Hill, Chapel Hill, NC27599；China

Abstract

Early restoration of blood flow to the ischemic myocardium not only saves myocardium but also induces reperfusion injury.While no specific therapy to reduce reperfusion injury has yet been established, recent laboratory studies have shown that G proteincoupled receptor (GPCR) agonists, insulin, and postconditioning can effectively prevent reperfusion injury in various experimental settings and animal species. The potential mechanisms underlying the cardioprotection initiated by these interventions may include activation of the reperfusion injury salvage kinase (RISK) pathway, inactivation of glycogen synthase kinase 3#beta# (GSK-3#beta#), and modulation of mitochondrial permeability transition pore (mPTP) opening. These encouraging laboratory findings may help us develop successful clinical strategies to salvage reperfused myocardium in patients with acute myocardial infarction.

Key words: Reperfusion injury;cardioprotection;G protein-coupled receptor;Insulin;ischemic postconditioning;mitochondrial permeability transition pore

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引用本文：

习瑾昆, 金元哲, 崔勋, 徐哲龙. 心肌再灌注损伤保护的机制和策略[J]. 生理学报 2007; 59 (5): 553-561.

Xi Jinkun, Jin Yuanzhe, Cui Xun, Xu Zhelong. Cardioprotection against reperfusion injury: updated mechanisms and strategies. Acta Physiol Sin 2007; 59 (5): 553-561 (in Chinese with English abstract).