心肌营养素－1(CT-1)是免疫性心肌损伤和微循环障碍的重要调控分子，有望成为自身免疫性心肌炎心力衰竭的干预靶点，但其作用机制尚不明确。我们在既往研究中提出了跨膜蛋白信号增强器的假设并验证了CT-1的促血管新生作用。七次跨膜蛋白ETBR具有信号增强器的特征，是信号传导的重要跨膜分子。基于前期研究我们提出CT-1可能通过ETBR跨膜蛋白的调控，导致Th1/Th2平衡、Treg/Th17失衡，促发级联反应及免疫失衡，通过血管新生、心肌肥大等干预自身免疫性心肌炎。本项目通过制备自身免疫性心肌炎大鼠模型、ETBR敲除大鼠模型及携带CT-1、ETBR及ETBR siRNA基因的慢病毒，以免疫损伤为切点，观察CT-1对心肌微血管内皮细胞信号通路的影响及实验性自身免疫性心肌炎的干预作用，探讨ETBR介导CT-1作用的细胞和分子机制，为CT-1干预自身免疫性心肌炎免疫性损伤和心力衰竭提供理论依据。

Cardiotrophin-1(CT-1) is an important regulator of immune myocardial injury and microcirculation disturbance.Cardiotrophin-1 is expected to be the target of the heart failure of autoimmune myocarditis,but the mechanism is not clear.In our previous study we proposed transmembrane protein signal enhancer hypothesis and verify the role of CT-1 in angiogenesis.The characteristics of the seven transmembrane protein endothelin receptor B(ETBR) is similar with signal enhancer,which is an important transmembrane signaling molecule .Based on previous studies we propesed that CT-1 is a target to treat autoimmune myocarditis. The mechanism may be regulation of seven transmembrane protein ETBR, leading to the Th1/Th2, Th17/Treg imbalance and trigger a cascade of reactions and immune imbalance ,realize its role through the process of angiogenesis, myocardial hypertrophy. We prepared rat autoimmune myocarditis model,ETBR knockout rat model and lentivirus carrying CT-1,ETBR and ETBR siRNA, immune injury was observed in the study.We observed the effect of CT-1 on the signaling pathways on myocardial microvascular endothelial cell and cardiac function of the autoimmune myocarditis rats.The role of ETBR in the CT-1 induced process were be studied,we also affirmed the molecular mechanism involved.