MFG-E8调节Th17/Treg细胞平衡在实验性自身免疫性心肌炎中的作用及相关机制研究

Autoimmune myocarditis is a serious hazard of common diseases to human health, is a kind of myocardial cells damage and releasing the myocardail globulin caused by virus infection, resulting in autoimmune myocardial inflammation. It is a major cause of dilated cardiomyopthy, heart failure, and other severe heart disease. Currently, there is still no specific treatment for autoimmune myocarditis. MFG-E8 is a kind of glycoprotein, and has a broad range of anti-inflammation and anti-apoptotic effects in different inflammatory disease. MFG-E8 regulating the balance of Th17/Treg cells plays a protective role in autoimmune diseases. Studies have shown that Th17 cell-mediated infiltration of inflammatory cell and secretion of inflammatory cytokine is a major cause of heart damage in autoimmune myocarditis, and JAKs/STATs is the key signaling pathways to the induction of Th17 cells differentiation. Preliminary experimental results of applicants showed that the serum concentration of MFG-E8 was negatively correlated with myocarditis. The topic intends to explore the anti-inflammatory/anti-apototic effects of MFG-E8 in inflammation factors induced myocardial cell injury, and to study that the MFG-E8 how to regulate Th17/Treg cells differentiation to reduce the damage of heart in the rat model of experimental autoimmune myocarditis through the signaling pathways of the JAKs/STATs.. Through the research in the project, we hope that would provide a new research perspective and a new target for prevention and treatment for inflammatory cardiomyopathy.

自身免疫性心肌炎是由于病毒感染而引起心肌损伤和心肌球蛋白释放从而导致自身免疫性心肌炎症，是造成扩张型心肌病、心力衰竭等重症心脏病的主要原因，目前仍无特效治疗手段。MFG-E8具有抗炎/抗凋亡的糖蛋白，其调节Th17/Treg细胞平衡在保护炎症性疾病具有重要作用。Th17细胞介导炎症细胞浸润及炎症因子表达是造成心肌炎的主要原因，而JAKs/STATs是诱导Th17细胞分化的信号分子。临床预实验表明，MFG-E8血清浓度与心肌炎呈明显负相关。居于此，本课题拟从细胞水平上探讨MFG-E8对炎症因子诱导H9c2心肌细胞损伤的抗炎/抗凋亡作用，并通过实验性自身免疫性心肌炎大鼠探讨外源性MFG-E8如何通过JAKAKs/STATs信号分子调节Th17/Treg细胞的分化，进而减轻自身免疫性心肌炎对心脏的损伤。经过本研究，希望可为心肌炎发病机制提供一些研究思路，并为临床心肌炎的预防和治疗提供一些新方法。

自身免疫性心肌炎是由于病毒感染而引起心肌损伤和心肌球蛋白释放从而导致自身免疫性.心肌炎症，是造成扩张型心肌病、心力衰竭等重症心脏病的主要原因，目前仍无特效治疗手段.。MFG-E8具有抗炎/抗凋亡的糖蛋白，其调节Th17/Treg细胞平衡在保护炎症性疾病具有重要作.用。Th17细胞介导炎症细胞浸润及炎症因子表达是造成心肌炎的主要原因，而JAKs/STATs是诱.导Th17细胞分化的信号分子。临床预实验表明，MFG-E8血清浓度与心肌炎呈明显负相关。居于.此，本课题拟从细胞水平上探讨MFG-E8对炎症因子诱导H9c2心肌细胞损伤的抗炎/抗凋亡作用.，并通过实验性自身免疫性心肌炎大鼠探讨外源性MFG-E8如何通过JAKAKs/STATs信号分子调节.Th17/Treg细胞的分化，进而减轻自身免疫性心肌炎对心脏的损伤。经过本研究，希望可为心.肌炎发病机制提供一些研究思路，并为临床心肌炎的预防和治疗提供一些新方法。