巨噬细胞介导的炎症反应参与心肌梗死后损伤与修复过程，是影响心力衰竭发生发展的重要原因，目前尚缺乏有效干预措施。我们首次发现名为IL-34的细胞因子在缺血性心肌病患者体内显著升高，与其预后相关，并能影响心梗后巨噬细胞的浸润和作用来介导心脏纤维化、加重心衰。本项目将进一步运用基因敲除小鼠、慢病毒感染等手段，从分子、细胞到动物层面明确IL-34通过CSF-1R受体经MEK1/2-ERK1/2通路介导巨噬细胞增殖极化，并从转录水平调控TGF-β的产生，进而激活成纤维细胞，促进胶原产生、心室重构的作用和机制。同时将从临床角度，阐明IL-34与急性心梗后心衰的关系，并证实IL-34中和抗体的治疗效果，为临床治疗提供新的靶点和策略，具有极大的临床应用前景和转化价值。

Macrophage-mediated inflammation is one of the most important factors in the development of heart failure, taking part in the injury and repair process after myocardial infarction. However, effective remedies remain limited. Our previous study first discovered the novel cytokine IL-34, significantly elevated in patients with ischemic cardiomyopathy and associated with its prognosis, could affect the infiltration and function of macrophages, thus aggravating cardiac fibrosis and deteriorating cardiac function..This project will use specific methods including knock out mice along with lentivirus infection to prove the function of IL-34 in the post-myocardial infarction period at different levels. We will also clarity the mechanism under which how IL-34 regulates the proliferation and polarization of macrophages as well as the production of TGF-β to activate fibroblasts and promote collagen deposition via MEK1/2-ERK1/2-associated pathway. Meanwhile, the relationship between IL-34 and the presence of heart failure after myocardial infarction, along with the therapeutic effect of anti-IL-34 antibodies will be clarified. Thus, our project aims to provide a novel target and therapeutic strategy on the treatment of heart failure, with application prospect and translation value.