SOCS3通过JAK2/STAT3通路调控巨噬细胞极化参与心肌炎向扩张型心肌病的演变

病毒性心肌炎迁延不愈可进展为扩张型心肌病（DCM），死亡率高。巨噬细胞促炎亚型M1和抑炎亚型M2比例失衡是其进展的重要机制。我们前期工作以及复习文献示，细胞因子信号途径抑制物3（SOCS3）调控JAK2/STAT3通路参与巨噬细胞向M1极化相关。因此提出假说：SOCS3可通过JAK2/STAT3通路调控巨噬细胞极化，参与心肌炎演变为DCM的过程。本研究拟在已有工作基础上，体外构建SOCS3过表达（转基因）和表达抑制（慢病毒沉默SOCS3基因）的骨髓来源巨噬细胞（BMDM）模型，观察调控SOCS3及其下游JAK2/STAT3通路对BMDM极化的影响；在体构建大鼠实验性自身免疫性心肌炎（EAM）模型，并将干预后的BMDM进行EAM大鼠在体回输试验，观察SOCS3是否可通过JAK2/STAT3通路调控BMDM极性进而干预EAM向DCM进展，为寻求心肌炎向DCM进展的防治靶点治疗提供新的科学依据。

The severe type of viral myocarditis which develops to dilated cardiomyopathy（DCM）with high mortality. The imbalance of macrophages pro-inflammatory subtype M1 and anti-inflammatory subtype M2 is the important mechanism of the progression. Our and other’s previous works showed: the suppressor of cytokine signaling 3 (SOCS3) may modulates the M1 polarization via JAK2/STAT3 pathway. So we propose the hypothesis: SOCS3 modulates macrophage polarization via JAK2/STAT3 pathway to influence the development from myocarditis to DCM. On the previous work basis, we intended to investigate influence of the bone marrow-derived macrophages (BMDM) polarization by SOCS3.overexpression(transgenic)/knockdown (lentiviral transfection) and to observe the effect on the BMDM polarization through regulation of SOCS3 expression and its downstream JAK2/STAT3 pathway in vitro; and to explore whether SOCS3 modulate BMDM polarization via JAK2/STAT3 pathway and then influence development from EAM（Experimental Autoimmune Myocarditis）to DCM in after injection the BMDM after modulating SOCS3 expression to EAM rats（who have the similar inflammatory progression to viral myocarditis in human）in vivo. The research will provide molecular evidence for potential treatment target of DCM induced by myocarditis.