APN转染BMSCs抑制TSP-1/TGF-β1介导的糖尿病心肌纤维化的研究

项目名称： APN转染BMSCs抑制TSP-1/TGF-β1介导的糖尿病心肌纤维化的研究

项目编号： No.81472149

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张晓明

作者单位： 浙江大学

项目金额： 80万元

中文摘要： 糖尿病已成为当今世界的高发疾病，其并发症如糖尿病心肌病等是糖尿病患者死亡主要原因之一。研究表明高血糖状态下心肌胶原增生和间质纤维化是患者心脏功能康复难题。脂联素（adiponectin,APN）作为脂肪细胞分泌的一种特殊蛋白，具有抗炎和抗纤维化作用。本课题组前期发现TSP-1/TGF-β1信号通路的激活是糖尿病大鼠心肌纤维化过程的中心环节，而给予APN治疗可显著减轻心肌纤维化。结合文献和我们先前实验结果，提出假说：APN可能通过调控TSP-1/TGF-β1通路来抑制糖尿病心肌胶原增生和间质纤维化过程。为此本研究拟采用骨髓间充质干细胞（BMSCs）作为APN的载体，采用体内糖尿病大鼠心肌病模型和体外高血糖细胞损伤模型，研究BMSCs旁分泌的APN 通过调控TSP-1/TGF-β1通路来抑制心肌纤维化、改善心肌间质结构、修复心脏功能的作用和机制，为糖尿病心肌病治疗和康复提供实验基础和理论依据。

中文关键词： 骨髓间充质干细胞；心脏康复；糖尿病心肌病；脂联素；TSP-1/TGF-β1

英文摘要： Diabetes is a high incidence of the disease in the world. The cardiovascular complications such as diabetic cardiomyopathy has become the leading cause of death in patients with diabetes. The pathological features of Diabetic cardiomyopathy were a significant reduction in myocardial cells, myocardial interstitial fibrosis and inter-collagen formation. Our Previously study found TSP-1/TGF-β1 signaling pathway play a key role on the cardiac fibrosis in diabetic rats. The results caused widespread concern and references. And adiponectin is a specific protein secreted by fat cells, could increase sensitivity of peripheral tissues to insulin, anti- atherosclerosis and fibrosis. Under Literature and our previous experimental results, this study will use bone marrow mesenchymal stem cells (BMSCs) as transfection carrier of APN for treatment of myocardial disease in diabetic rats and in vitro model of hyperglycemia myocardial injury, and observe TSP-1/TGF -β1 signaling pathway on the protective effect of these cells and heart from diabetic cardiac morphology, function and molecular biology science levels. It will provide some experimental evidence of rehabilitation of diabetic cardiomyopathy patients.

英文关键词： BMSCs;Cardiac Rehabilitation;diabetic cardiomyopathy;APN;TSP-1/TGF-β1