过刊浏览

腺苷和乙酰胆碱后适应诱导的心肌保护作用

臧伟进, 孙蕾, 于晓江

西安交通大学医学院药理学系心血管生理药理研究室.陕西,西安 710061

摘要

近年来缺血后适应的提出成为抗再灌注损伤的里程碑,其良好的临床可控性和可靠的保护效应引起人们广泛关注。缺血后适应即在心肌长时间缺血后再灌注之前,进行数次短暂的再灌注/ 缺血的循环处理,诱导产生心肌保护效应,其循环次数和间隔时间存在种属差异。研究证实后适应不仅限制急性期梗死面积,还可以减轻长期损伤,其是否与保护血管内皮、抑制中性粒细胞介导的氧化损伤相关还存在争议。上调再灌注损伤补救激酶(reperfusion injury salvage kinase, RISK)通路是后适应保护的重要机制之一,即激活磷脂酰肌醇--3 激酶(phosphatidylinositol 3--kinase, PI3K)--Akt 途径和/ 或细胞外信号调节激酶(extracellular signal--regulated kinase, ERK)途径,抑制线粒体通透性转换孔的开放,减少细胞凋亡和坏死。但是这两条途径的地位和关系还有待于进一步研究。为了更加适用于临床,研究者将机械调控转变为药物干预,观察药物能否模拟缺血后适应发挥保护作用,即药物后适应。腺苷是研究最广泛,也是最有希望成为临床正式用药的一种药物。作者实验室首先提出了乙酰胆碱可以模拟缺血后适应,通过线粒体ATP敏感钾通道发挥心肌保护效应。该文着重阐述缺血后适应保护缺血/再灌注损伤的效应和信号转导通路,尤其是腺苷和乙酰胆碱模拟药物后适应的可能机制和临床应用。

关键词： 后适应; 腺苷; 乙酰胆碱; 心肌保护; 丝裂原活化蛋白激酶; 细胞外信号调节激酶

Cardioprotection of ischemic postconditioning and pharmacological post--treatment with adenosine or acetylcholine

Zang Weijin, Sun Lei, Yu Xiaojiang

Division of Cardiovascular Physiology and Pharmacology, Department of Pharmacology, School of Medicine, Xi'an Jiaotong University.Xi'an 710061,Shaanxi

Abstract

The recent discovery of ischemic postconditioning is a landmark of anti-reperfusion injury. The medical community has a preference for postconditioning because it is easier to control in clinic and has reliable benefits to heart compared with preconditioning.Postconditioning is defined as a series of brief mechanical interruptions of blood flow applied at the very onset of reperfusion. It can reduce irreversible post-ischemic injury and protect myocardium. There are two important factors in the algorithm of postconditioning:cycle number and duration of intermittent episodes. The latter may depend on species and is more important than cycle number.Postconditioning-induced infarct-sparing effect persists not only after the acute phase of reperfusion but also after a prolonged reperfusion. However, whether cardioprotection of postconditioning is related to preservation of endothelial function and attenuation of oxidative damage is still under debate. Up-regulating the reperfusion injury salvage kinase (RISK) pathway is one of the mostimportant mechanisms in cardioprotection of postconditioning, including activation of phosphatidylinositol 3-kinase (PI3K)-Akt and/or extracellular signal-regulated kinase (ERK), which reduces apoptosis and necrosis by inhibiting the opening of mitochondrial permeability transition pore (mPTP). But the signal transduction of these two pathways needs further research. In order to be more suitable for clinical application, researchers translate mechanical maneuver into drug intervention to investigate whether drug can simulate ischemic postconditioning in cardioprotection, termed pharmacological postconditioning. Adenosine is one of the most extensive and prospective drugs in pharmacological postconditioning study. However, in our laboratory we demonstrate that acetylcholine is able to induce pharmacological postconditoning through mitochondrial ATP-sensitive potassium channel. The present article reviews the protective effects and signal transduction of postconditioning, especially the mechanisms and clinical application of adenosine- and acetylcholine-induced pharmacological postconditioning.

Key words: postconditioning;Adenosine;Acetylcholine;cardioprotection;mitogen-activated protein kinase;extracellular signalregulated kinase

收稿日期：　　录用日期：

通讯作者：　　E-mail:

引用本文：

臧伟进, 孙蕾, 于晓江. 腺苷和乙酰胆碱后适应诱导的心肌保护作用[J]. 生理学报 2007; 59 (5): 593-600.

Zang Weijin, Sun Lei, Yu Xiaojiang. Cardioprotection of ischemic postconditioning and pharmacological post--treatment with adenosine or acetylcholine. Acta Physiol Sin 2007; 59 (5): 593-600 (in Chinese with English abstract).