EAM发生经历“损伤-炎症-修复”三个阶段，既往工作证实抑制M1型Mφ极化或ANGII活性均能缓解EAM小鼠心肌损伤。预实验表明ANGII可诱导Ly6C(hi)向M1型Mφ分化/极化；且M1型Mφ分泌的细胞因子可激活成纤维细胞。由此提出“EAM时上调的ANGII诱导Ly6C(hi)单核细胞分化/极化为M1型Mφ导致心肌损伤、启动受损组织修复”的假说。为证实以上假说，本研究拟从体内外两方面进行：体外阐明ANGII调控Ly6C(hi)单核细胞分化机制以及M1型Mφ对成纤维细胞活化、增殖作用；体内通过对WT、Tyk2(-/-)、单核/Mφ选择性敲除小鼠模型诱导及ANGII再灌注与ANGII受体拮抗剂应用，阐明ANGII调控Ly6C(hi)单核细胞向M1型Mφ分化/极化参与EAM发生的机制。通过上述研究有望进一步阐明EAM发生过程，为心肌炎相关疾病的免疫干预治疗奠定基础。

The development of experimental autoimmune myocarditis (EAM) experienced three stages "injury-inflammatory-remodeling". Our previous work demonstrated that inhibition Mφ polarization or blockade angiotensin II (ANGII) could attenuate EAM progression. Our present data showed that ANGII induced Ly6C(hi) monocytes differentiation into M1 phenotype macrophage (Mφ); furthermore, cytokines produced by M1 phenotype Mφ could activate cardiac fibroblast. Therefore, we hypothesized that ANGII secreted by myocardial tissue promoted Ly6C(hi) monocytes differentiation into M1 phenotype Mφ, led to myocardial injury and involved in repair of injury myocardium. To confirm the above hypothesis, the project was carried out, in vitro, to clarify the mechanisms of ANGII modulating Ly6C(hi) monocytes differentiation into M1 phenotype Mφ; in vivo, EAM models were induced WT, Tyk2(-/-), monocytes/Mφ depletion BALB/c mice, respectively. And the heart and serum were collected and analyzed after the mice sacrifice. Additionally, ANGII reperfusion and ANGII receptor antagonists were also employed to confirm the above hypothesis. Following the project, we will expect to furthering confirm the process of myocarditis development and clarify the theory for intervention therapy of inflammatory diseases.