心肌缺血再灌注损伤（MIRI）介导的心肌细胞死亡，包括自噬性死亡（ACD）、凋亡、坏死三种形式。MIRI缺血期自噬开始上调，再灌注期过度激活的自噬转向ACD，加剧心肌损伤，因此阻断ACD是防治MIRI的关键。本课题组在证实心脏特异性miR-208a 经GATA4参与调控心梗后心肌重塑和阿霉素诱导的心肌细胞凋亡后，进行的预实验表明，阻断miR-208a显著减少自噬调节蛋白FoxO1表达，改善MIRI小鼠心肌细胞自噬和死亡。据此，我们推测：以miR-208a为靶点可调控自噬及MIRI，并拟建立MIRI模型，阐明miR-208a通过GATA4/FoxO1/Beclin-1轴调控心肌细胞自噬、ACD，继而影响MIRI的效应和具体机制，提出以miR-208a为靶点调控自噬防治MIRI的新思路，具有一定的理论创新和临床转化价值。

Cardiomyocyte death mediated by myocardial ischemia-reperfusion injury (MIRI) includes autophagic cell death (ACD), apoptosis and necrosis. However，over activation of autophagy leads to translation to ACD in reperfusion stage of MIRI, contributing to accelerated myocardial injury. Hence, blocking ACD is very important to prevent and treat MIRI. Our previous work showed that cardiac specific miR-208a plays a role in regulating ventricular remolding after myocardial infarction and doxorubicin induced myocyte apoptosis, mainly by targeting GATA4. Our preliminary study showed that blocking miR-208a significantly inhibits the expression of FoxO1, and ameliorates myocardial autophagy and death post MIRI. We deduce that targeting miR-208a can regulate autophagy and MIRI. MIRI model was induced to explore whether miR-208a could regulate GATA4/FoxO1/Beclin-1 pathway in autophagy and ACD and the exact mechanism how miR-208a regulate MIRI. In this study, we may provide a novel idea that targeting miR-208a can regulate autophagy for preventing and treating MIRI. This initiative has a value of theoretical innovation and clinical translation.