心梗后控制免疫炎症反应是当前防治慢性心衰的重要策略。通过线粒体Krebs循环重塑调控巨噬细胞极化，可能是控制心梗后免疫炎症的损伤-修复，改善心室重构关键途径。Krebs循环主要影响表观修饰来调控巨噬细胞极化，其在RNA水平的修饰尚未阐明。N6-腺苷酸甲基化（m6A）是在RNA中最普遍的表观修饰，FTO作为重要的去甲基化转移酶，能介导m6A修饰参与心衰的病理进程和心脏修复。申请人前期研究发现FTO介导m6A修饰可能是Krebs循环重塑调控巨噬细胞极化的重要机制。益气活血法利水法作为心衰的中医主要治法，可能通过影响Krebs循环重塑，作用于FTO介导m6A修饰来调控巨噬细胞极化，综合调控代谢-免疫炎症网络而防治心衰。本研究拟建立心梗致心衰动物模型，在动物和细胞水平探讨Krebs循环重塑通过FTO介导的m6A修饰对心衰巨噬细胞极化的影响，以及益气活血利水法代表方对该机制轴的影响及防治心衰的作用。

The control of immune inflammatory response after myocardial infarction is an important strategy for the prevention and treatment of heart failure. The regulation of macrophage polarization through mitochondrial Krebs circulation remodeling may be the key pathological pathway to control the injury-repair stasis after myocardial infarction and improve cardiac ventricular remodeling. Epigenetic modification is a major mechanism in the regulation of macrophage polarization through Krebs cycle reborn, but its modification at RNA level has not been elucidated. N6-Methyladenosine is the most abundant internal chemical modification in RNA. As an important demethylases, FTO can mediate m6A modification to participate in the pathological process and cardiac repair of heart failure. The applicant previously found that FTO-mediated m6A modification may be an important mechanism of Krebs cycle reborn in regulating macrophage polarization. As the main Chinese medicine treatment of heart failure, the method of benefiting qi, activating blood circulation and promoting diuresis may regulate the polarization of macrophages by affecting the reborn of Krebs circulation, acting on FTO-mediated m6A modification, thereby comprehensively regulate the metabolic-immune inflammatory network to prevent and treat heart failure. The purpose of this study is to establish an animal model of heart failure induced by myocardial infarction, and to explore the effect of Krebs cycle reborn on the polarization of macrophages via FTO mediated m6A modification in heart failure, and the effect of the representative formula of benefitting qi, activating blood circulation and promoting diuresis on this mechanism axis and its effect of prevention and treatment of heart failure at animal and cellular level.