急性心肌梗死（心梗）后心肌细胞凋亡可引起心脏舒缩功能障碍和心功能不全。研究表明自噬对缺氧心肌细胞凋亡有双向调控作用，然而具体机制不明。申请者前期小鼠及细胞研究证实：心肌缺氧早期产生适应性自噬，可减少细胞凋亡；抑制自噬则导致凋亡增加，最终损害心脏功能。通过生物信息学分析，发现心肌缺氧早期SIRT5基因变化显著，GO注释分析提示SIRT5与细胞凋亡直接相关；心肌细胞实验证实缺氧后SIRT5表达下调，氨浓度升高。近期研究发现SIRT5通过调控细胞内氨代谢，参与适应性自噬的调节。据此提出如下科学假说：缺氧后心肌细胞通过SIRT5调控氨代谢，诱导适应性自噬、抑制凋亡。为证实这一假说，申请者拟通过建立心梗小鼠模型及心肌细胞缺氧模型，采用腺病毒转染、蛋白荧光示踪等方法，从分子、细胞及动物多层面探究SIRT5对缺氧心肌自噬的作用，明确调控适应性自噬的机制。研究结果可为心肌梗死及缺血性心肌病治疗提供新思路。

Apoptosis of myocardial cells after acute myocardial infarction can cause cardiac dysfunction and cardiac insufficiency. Studies have shown that autophagy has a two-way regulation of hypoxia cardiomyocyte apoptosis, but the specific mechanism is unknown. Applicant's previous mouse and cell studies confirmed that adapted autophagy in early myocardial hypoxia can reduce cardiomyocyte apoptosis; inhibition of autophagy leads to increased apoptosis and ultimately impaired cardiac function. Through bioinformatics analysis, it was found that SIRT5 gene changed significantly in early myocardial hypoxia. Gene Oncology analysis suggested that SIRT5 was directly related to apoptosis. Cardiomyocyte experiments confirmed that SIRT5 expression was down-regulated and ammonia concentration was increased after hypoxia. Recent studies have shown that SIRT5 is involved in the regulation of adapted autophagy by regulating intracellular ammonia metabolism. Based on this, the following scientific hypothesis is proposed: after hypoxia, cardiomyocytes regulate ammonia metabolism through SIRT5 and induce adapted autophagy. In order to verify this hypothesis, the applicant intends to explore the regulation and mechanism of SIRT5 for hypoxic myocardium autophagy from molecular, cellular and animal multifaceted surfaces by establishing a myocardial infarction mouse model and a myocardium hypoxia model using adenovirus transfection and protein fluorescent tracing. The results can provide new ideas for the treatment of myocardial infarction and ischemic cardiomyopathy.