基于内源性保护通路的大蒜素后适应改善心肌缺血/再灌注损伤的分子机制研究

缺血/再灌注损伤是影响急性心肌梗死再灌注治疗预后的重要因素之一。采取有效措施清除氧自由基，激活内源性心肌保护通路，是减轻心肌细胞缺血/再灌注损伤的发生，减少梗死面积的重要途径。本课题组前期研究证实大蒜素能有助于减少猪急性心肌梗死面积，拟在前期研究基础之上,通过猪心肌缺血/再灌注损伤动物模型对大蒜素后适应介导的心肌内源性保护通路进行深入研究。同时以猪原代心肌细胞为切入点，围绕线粒体ATP敏感性钾通道、生存活化因子增强途径(SAFE)、再灌注损伤营救激酶途径(RISK)等，对大蒜素后适应发挥其心肌保护作用的机制及作用靶点进行深入探讨，旨在明确阐述大蒜素后适应防治心肌缺血/再灌注损伤的作用及其机制，为急性心肌梗死患者再灌注治疗及改善患者预后提供全新的干预手段和坚实的理论依据。

Ischemia/reperfusion (I/R) injury is one of the important factors which influence the effect of reperfusion treatment in the clinical setting. It is the important pathway to relieve I/R injury and reduce the myocardium infarct area by scavenging ROS effectively and promoting the endogenous cardioprotection pathway. It was proved in our previous studies that the infarct area was limited compared with control group by garlicin in swine I/R model. On the basis of the previous study results, further research in Chinese mini-swine I/R injury model will be promoted on the machenism of endogenous myocardial protecting pathway mediated by garlicin postconditioning. Meanwhile swine primary cardiomyocytes will be cultured to discuss the cardioprotective effect of postconditioning. Focusing on mitochondrial ATP-sensitive K+ channels (mitoKATP), reperfusion injury salvage kinase(RISK)pathway and survivor activating factor enhancement (SAFE) pathway, the mechanism and targets of garlicin postconditioning will be discussed and clarified to prevent myocardium I/R injury in molecular and cellar level. Our research will provide a new theoretical support on understanding the pathological mechanism of I/R injury and may contribute a lot in novel therapeutic strategy and theoretical evidence for acute myocardial infarction.