老龄是急性心肌梗死(AMI)发病的高危因素。我们最近利用心肌缺血再灌注（I/R）损伤模型，发现老龄加重心肌I/R损伤的敏感性，且巨噬细胞移动抑制因子MIF表达较年轻对照显著降低，但机制不清楚，MIF基因能特异性激活AMPK及ERK1/2信号通路，抵抗年轻心肌缺血损伤。据此，提出“MIF-AMPK/ERK1/2”级联信号通路调控心肌能量代谢、稳定线粒体功能的心肌内源性保护机制假说。本课题拟采用心肌I/R模型，探讨MIF在老龄心肌缺血损伤易感性中的作用机制；同时，利用重组MIF基因的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，揭示MIF基因靶向表达对抗老龄心肌缺血再灌注损伤的分子机制；基于老龄鼠体内外源导入MIF干预实验，确定MIF作为老龄心肌缺血再灌注损伤治疗靶标的效用，为减轻AMI患者缺血再灌注损伤、改善预后提供新的思路和依据。

Aging is considered as a major risk factor for acute myocardial infraction. Recently, we used myocardial ischemia-reperfusion injury mouse model, we found that the factor of aging increase the sensitivity to myocardial ischemia- reperfusion injury. The cardiac MIF protein expression significantly decreased when compared with the control group, but the mechanism is not clear, MIF gene can specifically activate AMPK and ERK1/2 signaling pathways to protect against young myocardial ischemic injury. Therefore, we hypothesize that the “MIF-AMPK/ERK1/2” cascade signaling pathway regulates the cardiac endogenous protective mechanism of energy metabolism and mitochondrial homeostasis. Accordingly, this study intends to use the model of myocardial ischemia-reperfusion injury to explore the susceptibility mechanism of MIF in aging related myocardial ischemia. Meanwhile, we construct the recombinant AAV9 vector which can targeted express MIF gene in heart. Via in vivo and in vitro transfection experiments, we can clarify the molecular mechanisms of MIF targeting expression reduce the myocardial ischemia injury at the cellular, tissue and whole animal level. Then based on intervention experiments of exogenous MIF importation in aging mice, the utility of MIF as ischemia-reperfusion injury therapeutic target of aging can be identified, it can also provide new ideas and basis to alleviate and improve the prognosis of ischemia-reperfusion injury in patients with acute myocardial infraction.