糖尿病心肌病（DCM）是2型糖尿病患者心力衰竭的主要原因，心肌纤维化是DCM特征性病理改变。T淋巴细胞亚群Th17/Treg失衡诱导的炎症反应在其中起重要作用。视黄醇结合蛋白4（RBP4）是新的促炎因子，我们前期发现RBP4可通过TLR4/MyD88通路促进心肌细胞胰岛素抵抗和病理性肥大；且RBP4水平在DCM小鼠升高，并与心肌纤维化及Th17/Treg失衡呈正相关。而TLR4/MyD88通路异常激活可促进Th17/Treg失衡。本项目将利用RBP4转基因和敲除小鼠糖尿病模型研究RBP4对糖尿病心肌纤维化的影响；并结合T淋巴细胞/心脏成纤维细胞共培养模型，研究RBP4是否通过诱导Th17/Treg失衡促进心肌纤维化；最后利用TLR4和MyD88敲除小鼠糖尿病模型研究RBP4是否通过TLR4/MyD88通路诱导Th17/Treg失衡，促进糖尿病心肌纤维化。本研究将为DCM的防治提供新思路。

Diabetic cardiomyopathy (DCM) is the major cause of heart failure in patients with type 2 diabetes. Cardiac fibrosis is the specific pathogenic feature of DCM. Imbalance of Th17/Treg induces cardiac inflammation, which plays crucial role in the process of diabetic cardiac fibrosis. Retinol binding protein 4 (RBP4) is a novel proinflammatory adipokine. Our previous studies showed that RBP4 promoted cardiac insulin resistance and pathogenic hypertrophy via inducing TLR4/MyD88 pathway. Moreover, serum RBP4 level was increased in mice with DCM, and positively correlated with the index of cardiac fibrosis and imbalance of Th17/Treg. It has been reported that TLR4/MyD88 pathway is involved in the development of Th17/Treg imbalance. Thus, our project will firstly construct type 2 diabetes model using RBP4 transgenic and knockout mice to investigate the role of RBP4 in diabetic cardiac fibrosis. Then T lymphocyte and cardiac fibroblast co-culture model will be used to explore whether RBP4 promotes diabetic fibrosis via inducing Th17/Treg imbalance. At last, we will construct type 2 diabetes model using TLR4 and MyD88 knockout mice to investigate whether TLR4/MyD88 pathway is involved in the promoting role of RBP4 in diabetic fibrosis. This proposal will provide a new insight into prevention and treatment for DCM.