由心肌炎发展来的炎性扩张性心肌病（iDCM）是导致心衰、猝死的重要原因，适时的控制炎症的消退成为控制心肌炎向iDCM进展的关键；实验性自身免疫性心肌炎（EAM）是研究由心肌炎演变为iDCM的有效模型。前期研究证实巨噬细胞（Mφ）在EAM炎症损伤、炎症消退以及向iDCM进展过程中扮演着重要的角色；预实验显示，5’-AMP抑制LPS/INF-γ诱导的TNF-α mRNA高表达，影响Mφ向炎性Mφ再编程，基于此提出“5’-AMP重塑心肌浸润Mφ功能，诱导炎症主动消退，延缓EAM进程”的假说。为证实这一假说，体外阐明5’-AMP对Mφ再编程的影响及其分子机制，体内通过使用CD11b-DTR巨噬细胞消融型小鼠以及5’-AMP的干预进一步阐明5’-AMP在EAM炎症消退过程中的机制。通过上述研究有望为心肌炎的防治提供新思路，并为嘌呤核苷酸在免疫调节中的作用提供新的研究方向。

An inflammatory dilated cardiomyopathy (iDCM) that develops from myocarditis has been shown to be an important cause of heart failure and sudden death; experimental autoimmune myocarditis (EAM) has been widely used as a valid model from myocarditis to developing iDCM. In our previous studies, macrophages (Mφ) play important roles in inflammatory injury, resolving inflammation, and progression to iDCM. 5’-AMP reduced LPS/INF-γ-induced high expression of TNF-α in Mφ, inhibiting the reprogramming of Mφ into inflammatory Mφ. These results suggested that 5’-AMP reprograms the functions of cardiac infiltrating Mφ, leading to pro-resolving inflammation, and delay the development of EAM. In this project, we will investigate the effects of 5’-AMP on Mφ reprogramming and explore the molecular mechanisms in vitro. In vivo, we will investigate the mechanisms for pro-resolving inflammation by 5’-AMP in mice with EAM, which are macrophage ablation in CD11b-diphtheria toxin receptor transgenic mice. This project will indicate a potential preventive and therapeutic strategy for myocarditis, and our findings will be important to further understanding of the functions of purinergic signaling in immunoregulation.