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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。我们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。本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。
In recent years, the proposed post-ischemic adaptation has become a milestone in anti-reperfusion injury, and its good clinical control and reliable protective effect aroused widespread concern. Ischemic postconditioning involves reperfusion / ischemia of the myocardium several times before reperfusion after a long period of ischemia and induces a cardioprotective effect. The number of cycles and intervals vary. Studies confirm that postconditioning not only limits acute infarct size, but also long-term damage, whether it is related to the protection of vascular endothelium, inhibition of neutrophil-mediated oxidative damage is still controversial. Up-regulation of the reperfusion injury salvage kinase (RISK) pathway is one of the important mechanisms of postconditioning protection, that is, activation of the phosphatidylinositol 3-kinase (PI3K) -Akt pathway and / or extracellular The signal transduction kinase (ERK) pathway inhibits the opening of the mitochondrial permeability transition pore and reduces apoptosis and necrosis. However, the status and relationship of these two channels have yet to be further studied. In order to be more suitable for clinical use, the researchers turned mechanical regulation into drug intervention, and observed whether the drugs could simulate the protective effect after the ischemic adaptation, that is, after drug adaptation. Adenosine is the most widely studied and most promising drug for clinical use. Our laboratory first proposed that acetylcholine mimic ischemic postconditioning and exert a cardioprotective effect through mitochondrial ATP-sensitive potassium channels. This article focuses on the possible mechanism and clinical application of post-ischemic adaptations to protect against ischemia-reperfusion injury and signal transduction pathways, particularly post-adaptation to adenosine and acetylcholine mimics.