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线粒体乙醛脱氢酶在心肌缺血再灌注中的作用——从实验台到临床

庞佼佼, Linzi A. Barton, 陈玉国, 任骏

怀俄明大学健康科学学院心血管研究与转化医学中心，拉勒米 WY 82071，美国；山东大学齐鲁医院急诊科，济南250012；复旦大学中山医院上海心血管病研究所，上海 200032

摘要

急性心肌梗死是目前严重威胁人类健康的致死疾病之一，及时再灌注是限制心肌梗死面积的最有效方法，然而，再灌注本身会导致进一步的心肌损伤。线粒体乙醛脱氢酶(mitochondrial aldehyde dehydrogenase, ALDH2)被广泛熟知为代谢乙醛的酶。越来越多的证据表明ALDH2在心肌缺血再灌注中起到心肌保护的作用。动物实验表明ALDH2可减少心肌梗死面积，减轻心功能紊乱，防止再灌注性心律失常的发生。突变型ALDH2*2基因编码的ALDH2酶活性显著降低，而该基因的突变率在亚洲人群中约为40%。在亚洲人中的流行病学调查表明，ALDH2基因多态性与急性心肌梗死面积和冠状动脉疾病发生率紧密相关。因此，将ALDH2作为治疗心肌缺血再灌注损伤的靶点将很有前景。本文综述ALDH2对缺血再灌注心肌的保护作用及机制，并探讨 ALDH2的转化应用研究前景。

关键词： ALDH2; 心肌缺血再灌注损伤; 4-HNE; 凋亡; 自噬; 线粒体损伤; 内质网应激

分类号：R541.4

Mitochondrial aldehyde dehydrogenase in myocardial ischemia-reperfusion injury: from bench to bedside

PANG Jiao-Jiao, Linzi A. Barton, CHEN Yu-Guo, REN Jun

Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA； Department of Emergency, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China； Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Abstract

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.

Key words: ALDH2; myocardial ischemia-reperfusion; 4-HNE; apoptosis; autophagy; mitochondrial injury; ER stress

收稿日期：2015-05-20　　录用日期：2015-09-09

通讯作者：陈玉国,任骏　　E-mail: chen919085@126.com,

引用本文：

庞佼佼, Linzi A. Barton, 陈玉国, 任骏. 线粒体乙醛脱氢酶在心肌缺血再灌注中的作用——从实验台到临床[J]. 生理学报 2015; 67 (6): 535-544.

PANG Jiao-Jiao, Linzi A. Barton, CHEN Yu-Guo, REN Jun. Mitochondrial aldehyde dehydrogenase in myocardial ischemia-reperfusion injury: from bench to bedside. Acta Physiol Sin 2015; 67 (6): 535-544 (in Chinese with English abstract).