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再灌注心脏保护的新策略：后处理和预处理的比较(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2006年第1期
页码:
1-7，13
栏目:
专家论坛
出版日期:
2006-01-01

文章信息/Info

Title:
Alternative cardioprotective strategy during reperfusion: postconditioning vs preconditioning
作者:
赵志青1; 臧益民2
1. 艾默蕾大学医学院卡莱尔·费莱舍心脏中心心胸研究实验室，美国乔治亚州 亚特兰大; 2.第四军医大学生理学教研室，陕西 西安 710032
Author(s):
ZHAO Zhi-qing1; ZANG Yi-min2
1.Cardiothoracic Research Laboratory, The Carlyle Fraser Heart Center/Crawford Long Hospital, Emory University School of Medicine, Atlanta, Georgia, USA; 2. Department of Physiology,Fourth Military Medical University,Shaanxi,Xi′an 710032,China
关键词:
后处理; 预处理; 缺血/再灌注; 损伤; 心脏
Keywords:
postconditioning;  preconditioning;  ischemia/reperfusion injury;  heart
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
心肌缺血/再灌注引起的损伤（RMMI）是由多种触发物、媒介物和效应器参与的复杂生物反应过程，导致炎症反应、内皮细胞损伤、血流障碍、心功能异常、心肌细胞坏死和凋亡。过去二十多年来，尽管人们开发了多种心脏保护措施（药物性干预）以减少RMMI，但结果并不令人满意。因此，在临床上寻求可行和有效的治疗措施以减轻RMMI有着极大的价值。我们实验室近来报道了在再灌注或恢复供氧早期，快速反复中断冠脉血流或氧供（缺血或缺氧后处理），可减少心肌组织或细胞内自由基的生成，减轻钙超载，减轻内皮功能的损伤，降低黏附蛋白的表达，减少坏死和凋亡。后处理的这些保护作用可能和内源性生成物如腺苷和一氧化氮增多、蛋白酶（包括PI3KAkt和ERK1/2)的激活、线粒体的ATP依赖性K+通道开放和线粒体通透性转换孔关闭有关。与预处理比较，后处理具有同样的保护效应。在长时间再灌注后仍有减少梗死范围的作用。目前的实验结果和临床观察证实，在缺血后恢复血供时，后处理的应用在治疗缺血/再灌注损伤方面开启了一个新的治疗窗口。
Abstract:
Reperfusion of ischemic myocardium is a complex biological process that involves multiple triggers, mediators and endeffectors, resulting in inflammatory and endothelial damage blood flow defects, cardiac dysfunction, necrosis and apoptosis. In the last two decades, although considerable effort has been exerted in exploring cardioprotective strategies in an attempt to limit reperfusioninduced myocardial injury, most of the clinical trails using various pharmacological agents to attenuate reperfusion injury have been rather unsatisfactory. Therefore, it is extremely valuable to explore some clinically feasible and effective therapeutic strategies that address postischemic myocardial injury. Reduction in infarct size and cell death with rapid sequential intermittent interruption of coronary blood flow or oxygen supply at the beginning of reperfusion or reoxygenation (i.e. ischemic or hypoxic postconditioning) has been recently reported by our laboratory. The protection with postconditioning was expressed as reduction in generation of superoxide radicals, calcium overload, endothelial dysfunction, adhesion molecule expression, necrosis and apoptosis. Mechanisms by postconditioning have been associated with preservation of endogenous autacoids such as adenosine and nitric oxide, activation of protein kinases including PI3KAkt and ERK1/2, opening of mitochondrial KATP channels and closing of mitochondrial transition permeability pore. Reduction in infarct size by postconditioning was largely preserved after a prolonged reperfusion and this novel strategy achieved cardioprotection that was comparable to conventional ischemic preconditioning. Experimental studies and clinical observations to date have demonstrated that application of postconditioning at the onset of recovery of blood flow after ischemia opens a new therapeutic strategy in the treatment of ischemia/reperfusion injury.

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备注/Memo

备注/Memo:
收稿日期：2005-09-27.Supported by: grant from the National Institute of Health (HL64886) and funds from the Carlyle Fraser Heart Center of Emory University School of Medicine. Correspondence to: ZHAO Zhiqing, M.D., Ph. D. Tel: 4046862511Email: zzhao@emory.edu
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