糖尿病心肌病（DCM）是糖尿病患者发生心衰的重要原因，其发生机制不清。最近研究发现，CD4+T细胞在心脏组织的募集是心室重构和功能障碍的重要因素。RAS异常激活是糖尿病炎症反应的起始因素。T细胞表达AngⅡ的受体AT1R。我们发现Ⅱ型糖尿病模型小鼠心肌组织中CD4+T细胞明显增加，并与心功能密切相关，因此推测，糖尿病异常激活的RAS可能通过AT1R促进CD4+T细胞在心肌组织的募集并介导DCM的发生。本研究将建立HFD+STZ诱导的糖尿病小鼠模型，抗CD4单抗去除体内CD4+T细胞，AT1R抑制剂阻断RAS系统，评价CD4+T细胞募集和RAS对心功能，心脏病理改变的作用。QPCR,流式细胞术和组化等分析心肌组织炎症反应以及RAS对CD4+T细胞表型和功能的影响，WB和趋化因子蛋白芯片等评价RAS激活CD4+T细胞并介导其在心肌组织募集和效应的机制，可能为后续探索有效的干预策略提供实验依据。

Diabetic cardiomyopathy（DCM）is associated with substantial risk of heart failure and increased mortality in patients with diabetes. Mechanisms of DCM progression remain elusive. Compared to other tissues,RAS is highly expressed in the heart. Excessive activations of RAS play vital roles in initiation of the diabetic inflammation. Recent findings revealed that localization of CD4+T cells in the heart contribute to the myocardial remodeling and dysfunction. Our recent data showed cardiac dysfunction and increased infiltration of CD4+ cells in the heart of diabetic mouse model. Therefore, we hypothesize that over-activation of RAS in diabetes promote the homing of CD4+T cells to the heart and the function of these CD+ T cells contribute to the DCM progression. In the present study, type Ⅱ diabetic mouse models were established using HFD and STZ. To define the role of CD4+ T cells in DCM in vivo, anti-CD4 antibody will be used to deplete the CD4+ T cells. To determine whether RAS lead to the activation and migration of CD4+ T cells, AT1R inhibitor will be injected to diabetic mice to block the function of AngⅡ. Through analyzing the degree of myocardic remodeling by histology and immunohistochemistry, detecting the levles of inflammatory cytokines and CD4+ T cells phenotype and function by flow, QPCR and ELISA and evaluating the state of activation of signal pathway and chemokine receptors profile by western blot and protein chip, we can reveal the mechanism in which CD4+ T cells migrate and act locally to aggravate DCM. This project would provide new data for the therapy and intervention of DCM.