在炎症性扩张型心肌病（iDCM）中，巨噬细胞通过影响心肌炎症反应发挥关键作用。然而，iDCM中巨噬细胞的来源和调控机制仍不完全清楚。A类清道夫受体（SR-A1）通过调控巨噬细胞的生物学活性，参与多种疾病进程。本课题组前期研究发现，小鼠在盐酸阿霉素的诱导下，组织源性巨噬细胞增殖增多，且以M2型为主；SR-A1-/-小鼠更易产生iDCM的典型病理表现。因此我们认为，SR-A1可能通过调控巨噬细胞的募集、增殖以及极性分化，影响iDCM的进程。本研究拟通过比较野生型与SR-A1-/-小鼠心肌组织中巨噬细胞的来源，募集、增殖和极性分化上的差异，明确SR-A1在iDCM进程中的作用，在此基础上，进一步应用液相色谱-质谱联用，筛选iDCM中SR-A1的特异性配体，明确其调控巨噬细胞功能的具体作用机制。本研究将为寻找iDCM临床治疗的靶点，提高诊治水平提供理论依据。

Inflammatory dilated cardiomyopathy (iDCM) is among the most common causes of noncongenital heart failure in individuals under the age of 40. Myocardial inflammation plays a crucial role in the pathogenesis of cardiomyopathy, in which modulation of macrophage activities is a key pathological process. However, the modulating mechanism of macrophages in myocardium is not fully understood. Class A1 scavenger receptor (SR-A1) is an important pattern recognition receptor implicated in regulation of macrophage activities. We found that SR-A1 protects murine myocardial infraction through regulation of macrophage polarization in previous research, indicating that SR-A1 may participate in the regulation of the myocardial inflammatory microenvironment. Our preliminary research also showed that local macrophage proliferation dominates M2 macrophage during doxorubicin induced murine iDCM and SR-A1 deficiency could enhance the iDCM progression. Thus, we hypothesized that SR-A1 participate in the regulation of iDCM through modulating macrophage proliferation, recruitment and function. In this project, we will investigate the role of SR-A1 in macrophage activities and its impact on dilated cardiomyopathy by means of in vivo and in vitro experiments. The aim of our study is to discover novel endogenous ligand for SR-A1 and elucidate molecular mechanisms underlying macrophage infiltration, proliferation and polarization in myocardial inflammation. This study will be helpful in providing new therapeutic targets for cardiomyopathy diseases.