动脉粥样硬化（AS）是冠心病的基本病因。我们最近利用ApoE基因敲除AS小鼠模型，发现AS病理变化加重心肌缺血再灌注损伤的敏感性，且心肌ERK1/2通路活性较健康对照组显著降低，但机制不清楚，CaMEK 基因能特异性激活ERK1/2信号通路，抵抗心肌缺血损伤。据此，本课题拟采用心肌缺血再灌注损伤模型，探讨ERK1/2通路在AS心肌缺血损伤易感性中的作用机制；同时，构建快速表达CaMEK基因的双链重组AAV9载体，通过体内外转染实验，在细胞、组织及动物整体水平上，明确CaMEK对ERK1/2通路关键靶基因的调控，揭示ERK1/2通路激活抵抗心肌缺血损伤的分子机制；基于AS鼠体内外源导入CaMEK干预实验，阐明靶向激活心肌ERK1/2通路防治AS心肌缺血再灌注损伤的效果及分子机制，确定外源CaMEK作为AS心肌缺血损伤治疗靶标的效用，为减轻冠心病患者缺血再灌注损伤、改善预后提供新的思路和依据。

Atherosclerosis (AS) is the basic cause of coronary heart disease. Recently, we used ApoE knockout AS mouse model, we found that the pathological changes of AS increase the sensitivity to myocardial ischemia-reperfusion injury. The cardiac ERK1/2 pathway activity significantly decreased when compared with the healthy control group, but the mechanism is not clear, CaMEK gene can specifically activate ERK1/2 signaling pathway to protect against myocardial ischemic injury. Accordingly, this study intends to use the model of myocardial ischemia-reperfusion injury to explore the susceptibility mechanism of ERK1/2 pathway in AS related myocardial ischemia. Meanwhile, we construct the double-stranded recombinant AAV9 vector which can express CaMEK gene rapidly. Via in vivo and in vitro transfection experiments, we can clarify regulated role of CaMEK in critical target genes of ERK1/2 pathway at the cellular, tissue and whole animal level. Then molecular mechanisms of the ERK1/2 pathway activation against the myocardial ischemia injury could be revealed. Based on intervention experiments of exogenous CaMEK importation in AS mice, we can clarify the effects and molecular mechanisms of ERK1/2 signaling pathway targeted activation in the prevention of myocardial ischemia-reperfusion injury of AS. The utility of exogenous CaMEK as myocardial ischemia therapeutic target of AS can be identified, it can also provide new ideas and basis to alleviate and improve the prognosis of ischemia-reperfusion injury in patients with coronary heart disease.