内源性心肌再生是防治心肌梗死后心力衰竭新的治疗手段。当前的再生靶点忽略了支持心肌增殖存活的免疫微环境，使得心肌再生难以持续，导致对心功能长期改善效果不佳。极化的M2型巨噬细胞具有改善心肌免疫微环境，促进心脏受损后再生修复的作用。既往促巨噬细胞极化手段存在对细胞、组织特异性差以及极化效率低等缺点，我们前期研究筛选出心脏特异高表达的有调控巨噬细胞向M2型极化和心肌增殖潜能的环状RNA（circRaf1）。因此假设：circRaf1调控巨噬细胞极化改善心肌免疫微环境促进心梗后心脏再生。本项目拟在小鼠心尖切除及心梗模型上，采用免疫荧光、功能获得/缺失及遗传谱系追踪等方法：A. 验证筛选出的circRaf1可特异诱导心脏驻留巨噬细胞向M2型极化并促进心脏再生；B. 阐明circRaf1诱导M2型巨噬细胞极化介导心脏再生的具体分子机制。本项目将为临床改善心梗后心力衰竭提供更加有效的新靶点和理论依据。

Endogenous myocardial regeneration is a novel strategy for preventing heart failure after myocardial infarction. Current genetic targets ignore the immune microenvironment that sustains myocardial proliferation and survival, which makes myocardial regeneration difficult to restain, leading to poor long-term improvement of heart function. Polarized M2 macrophages have the effect to improve the immune microenvironment and promote cardiac regeneration and repair after myocardial injury. Previous approaches of stimulating polarization of macrophages have the disadvantages of poor cell and tissue specificity and low polarization efficiency. In our previous research, we screened out cardiac-specific high expressed circular RNA (circRaf1) that have the potential to induce macrophages to polarize to M2 and promote cardiomyocyte proliferation. Therefore, we hypothesized that circRaf1 promoted cardiac regeneration after myocardial infarction by regulating macrophage polarization and improving cardiac immune microenvironment. This project intends to adopt immunofluorescence, function acquisition/deletion, and genetic lineage tracking methods: A. verify that the screened circRaf1 can specifically induce cardiac resident macrophages to polarize to M2 type and improve heart regeneration efficiently; B. elucidate the underlying molecular mechanism of circRaf1 mediating heart regeneration in mouse apical resection and myocardial infarction models. This project will provide more effective new target and theoretical basis for clinical improvement of heart failure after myocardial infarction.