病毒性心肌炎向扩张型心肌病演变过程中Th22细胞对心肌纤维化的作用研究

病毒性心肌炎（VMC）和扩张型心肌病（DCM）临床常见，约20% DCM由VMC演变，被视为同一疾病的不同病理阶段，心肌纤维化是VMC发展为DCM的病理基础。Th22细胞参与多种自身免疫疾病纤维化形成。本课题组发现VMC小鼠心肌IL-22 mRNA显著升高，而Th22是否参与VMC向DCM进展过程心肌纤维化尚不清楚。本项目建立小鼠VMC及DCM模型，用流式细胞术等方法检测不同时期Th22及其相关因子改变；用抗IL-22抗体、IL-22-/-小鼠阻断IL-22作用，观察心肌纤维化及相关因子变化；用体外培养方式检测IL-22及其作用信号通路分子STAT3对心脏成纤维细胞增殖及分泌相关纤维化因子的影响。观察小鼠VMC进展至DCM过程Th22细胞的变化规律、探讨Th22及其作用信号通路分子STAT3对心肌纤维化的作用。本项目对阐明VMC向DCM演变过程中心肌纤维化机制和寻求新的防治靶点有重要意义。

Viral myocarditis(VMC) and dilated cardiomyopathy (DCM) are common cardiac diseases. About 20% individuals with VMC will evolve into DCM. Researchers have suggested that VMC and DCM may represent the different pathological stages of a same disease. But the possible mechanism by which VMC progressing to DCM has not been postulated.Myocardial fibrosis is considered as a major determinant that contributes to the development from VMC to DCM. However mechanisms of which are not well addressed.Emerging data have show that Th22 cells participate in in?ammatory responses and fibrosis of autoimmune disease. Our data show that cardiac IL-22 mRNA increased siganificantly in mice VMC,but whether Th22 cell involve in myocardial fibrosis which in the progressing from VMC to DCM remain to be determined.In this study, mice are used to induced VMC and DCM model.The expression of Th22 cells and its major cytokine were assessed in different stage from VMC to DCM; anti-IL-22 antibody and IL-22-/- mice were used to block the pathogenic role of IL-22,whose major function is STAT3-dependent, myocardial fibrosis and Th22 major cytokine were assessed;the effect of IL-22 and STAT3 to myocardial fibroblasts were measured by cultruing in vitro,and major cytokine about myocardial firosis were detected in protein and mRNA level.This study aims to investigate the dynamic alterations of Th22 cells in the course from VMC to DCM, explore the role of Th22 cells and STAT3 in myocardial fibrosis，thus elucidate the pathogenesis of myocardial fibrosis in the progressing from VMC to DCM, and provide new evidence for potential therapeutic target.