Cohen M V, Downey J M
Department of Medicine, University of South Alabama, College of Medicine, Mobile 36688, USA.
Annu Rev Med. 1996;47:21-9. doi: 10.1146/annurev.med.47.1.21.
In the phenomenon termed "ischemic preconditioning," a brief period of ischemia prior to a more prolonged one improves myocardial function (after reperfusion) and diminishes infarction. This phenomenon has been described extensively in experimental animals and now in humans. It is triggered by several agents released by ischemic cells and can be reproduced by infusion of agonists coupled to protein kinase C (PKC), e.g. adenosine, angiotensin, phenylephrine, bradykinin, and endothelin. The intracellular signaling pathway involves a phospholipase, either C or D, which metabolizes membrane phospholipids to produce diacylglycerol, a necessary endogenous cofactor for PKC activation. Which protein(s) is phosphorylated by PKC is not yet known, nor is the identity of the end-effector that actually mediates protection of the ischemic cell. Identification of the end-effector may make it possible in the routine treatment of patients with ischemic heart disease to precondition and thereby salvage ischemic myocardium and improve survival.
在被称为“缺血预处理”的现象中，在较长时间缺血之前的一段短暂缺血会改善（再灌注后的）心肌功能并减少梗死面积。这种现象在实验动物中已得到广泛描述，现在在人类中也有相关报道。它由缺血细胞释放的几种因子触发，并且可以通过输注与蛋白激酶C（PKC）偶联的激动剂来重现，例如腺苷、血管紧张素、去氧肾上腺素、缓激肽和内皮素。细胞内信号传导途径涉及磷脂酶C或D，其代谢膜磷脂以产生二酰基甘油，这是PKC激活所必需的内源性辅助因子。PKC使哪些蛋白质磷酸化尚不清楚，实际介导缺血细胞保护作用的终效应器的身份也不清楚。确定终效应器可能使缺血性心脏病患者的常规治疗中进行预处理从而挽救缺血心肌并提高生存率成为可能。
