心肌缺血再灌注损伤是围术期发生心血管事件的主要原因之一，线粒体凋亡是其重要机制，FOXO4转录调控基因参与了此过程。有研究发现miR-499a-5p抑制线粒体凋亡和减轻心肌梗死。我们的预实验提示：心肌缺氧复氧时，心肌细胞发生凋亡，miR-499a-5p表达降低，FOXO4表达增加。为此，我们推测miR-499a-5p可能通过靶基因FOXO4来调控线粒体凋亡而发挥心肌保护作用的。为验证该假说，我们通过细胞缺氧复氧和在体缺血再灌注模型，采用共聚焦显微镜、qRT-PCR、Western blot、RNA干扰等方法，从分子、细胞和整体分别来明确miR-499a-5p和FOXO4对线粒体凋亡的调控作用，同时进一步通过双荧光素酶靶基因检测、基因沉默、慢病毒过表达等技术，深入研究miR-499a-5p与靶基因FOXO4的结合位点，以及该靶向作用对线粒体凋亡的调控机制，为围手术期心肌保护提供新的理论依据。

Myocardial ischemia-reperfusion injury is the leading cause for perioperative cardiac events. During this process, mitochondrial apoptosis accounts for its main mechanism, and FOXO4 transcription gene takes an important part. Studies found that miR-499a-5p inhibited mitochondrial apoptosis and alleviated myocardial infraction. Our preliminary experiments showed excessive apoptosis with miR-499a-5p downregulation and FOXO4 upregulation in cardiomyocyte exposed to hypoxia-reoxygenation. Therefore, we hypothesize that miR-499a-5p protects the heart against ischemia-reperfusion injury by regulating mitochondrial apoptosis via targeting FOXO4 dependent mechanisms. To test this hypothesis, we evaluate the role of FOXO4 and miR-499a-5p in regulation of mitochondrial apoptosis under the in vivo model of myocardial ischemia-reperfusion injury in rats and in vitro model in primary neonatal rat cardiomyocytes by using various methods including confocal microscopy, qRT-PCR, Western Blot, and RNA interference. Furthermore, we investigate the binding site of miR-499a-5p targeting FOXO4 gene and the underline mechanisms for regulating mitochondrial apoptosis by using various methods including Luciferase gene detection, gene silence, and lentivirus overexpression. We aim to demonstrate that miR-499a-5p provides cardioprotection by inhibition of mitochondrial apoptosis via FOXO4 dependent mechanisms in order to provide new ideas and theoretical basis for perioperative cardioprotection.