线粒体自噬失衡是介导糖尿病心肌梗死后心肌损伤的关键环节，研究证实O亚型叉头框蛋白1（FOXO1）是调控线粒体自噬的关键因子，但其在糖尿病心梗后心肌损伤中的作用尚不清楚。过氧化物酶（peroxidasin，PXDN）是本课题组证实高表达于心脏组织中的过氧化物酶家族成员，申请人前期研究发现PXDN在心梗后心肌修复期明显升高，其通过诱导氧化应激介导了心梗后心肌纤维化。本项目前期研究发现与非糖尿病心梗相比，糖尿病心梗小鼠的心肌组织中PXDN表达在心梗早期即显著升高，同时FOXO1磷酸化增加及线粒体自噬失衡，提示PXDN可能通过调控线粒体自噬参与糖尿病心梗后心肌损伤过程。因此，本项目拟在利用基因模式动物确证PXDN介导糖尿病心梗后心肌损伤基础上，结合基因技术及工具药物阐明PXDN调控线粒体自噬的具体机制。本项目将为PXDN在心肌损伤中的作用提供新的认识，并为寻找新的干预靶点提供实验依据。

The imbalance of mitophagy is a key contributor of myocardial injury in myocardial infarction (MI) combined with diabetes mellitus (DM). It has been demonstrated that forkhead box O1(FOXO1) is an important mediator of mitophagy. However, the role of FOXO1 in myocardial injury after MI with DM remains unknown. Peroxidasin (PXDN), a member of peroxidase family, is identified by our group, which is highly expressed in situ in heart tissue. Our previous studies have demonstrated that the expression of PXDN is significantly increased in reparative phase, which contributes to fibrosis after MI. Our preliminary data shown that the expression of PXDN and phosphorylation of FOXO1 in myocardial tissues of MI mice with DM is obviously increased and the imbalance of mitophagy is occurred in early stage of MI, compared with that in MI mice with no DM. These results suggest that PXDN maybe participate in myocardial injury after MI with DM through regulating mitophagy. Therefore, this study is aimed to confirm that PXDN contributes to myocardial injury in MI with DM by using genetic mice, and elucidate the mechanism of PXDN regulating mitophagy by using gene technology. This project will provide a new understanding of the role of PXDN in myocardial injury and experimental basis for finding new intervention targets.