OSMR在糖尿病心肌病中的作用和机制研究

项目名称： OSMR在糖尿病心肌病中的作用和机制研究

项目编号： No.81470374

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： 罗鹏程

作者单位： 武汉大学

项目金额： 68万元

中文摘要： 强化降糖治疗并不能降低糖尿病心肌病（DCM）的发生率,增强心肌修复能力可能是治疗DCM的新途径。抑瘤素M(OSM)可通过其特异性受体OSMR调节心肌细胞去分化和重组，达到修复功能；前期我们发现OSMR在糖尿病小鼠心肌中降低，OSMR敲除小鼠给予高脂饮食其血糖和心功能恶化程度大于对照，说明OSMR可能具有调节血糖和直接参与心肌修复的作用。本项目拟从细胞、动物、分子水平阐述OSMR在DCM中的作用和机制：1.通过OSMR腺病毒载体在大鼠原代心肌细胞过表达和沉默OSMR基因，给予高糖刺激建立DCM模型，研究OSMR在糖尿病心肌病中的作用和机制；2.通过高脂饮食和链佐菌素在特异性心肌敲除和过表达OSMR小鼠中建立DCM模型，进一步研究其在血糖稳态和心肌修复中的作用和机制；3.通过药物或基因工程调节OSMR下游调节DCM的关键分子以期逆转OMSR敲除和过表达的表型；为DCM的防治提供理论基础。

中文关键词： 糖尿病心肌病；OSMR；去分化；信号通路；转基因

英文摘要： Lowing blood glucose therapy is limited for diabetic cardiomyopathy(DCM), enhancing the self-repairment ability of cardiomyocytes is an alterative strategy.OSMR is the receptor of oncostatin M, which regulates cardiomyctye dediffereniation and reorganization.Our preliminary data show that OSMR is decreased in obesity mice and OSMR knockout exhibited a worsen blood glucose and heart function.These findings indicate that OSMR may be invovled in glucose homestasis and cardiomyocyte self-repairment .This project will explore the role of OSMR in diabetic cardiomyopathy from the following 3 aims: 1).we will explore the role and mechansim of OSMR by overexpression and knockdown of OSMR in rat primary cardiomyocytes stimulated by high glucose;2).by using cardiomyocyte-specific OSMR knockout and transgenic mice treated with high fat diet and streptozotocin; 3). We will block and activate the key downstream signaling of OSMR using related drugs and genetic engineering to reverse the phenotype results by OSMR knockout and transgenic. This project may provide a new strategy for the OSMR prevention and therapy.

英文关键词： Diabetic Cardiomyopathy;OSMR;Dedifferentiation;Signaling Pathway;Transgene