尾加压素Ⅱ/氧化应激/内质网应激在糖尿病性心肌病心肌细胞凋亡中的作用及分子机制

项目名称： 尾加压素Ⅱ/氧化应激/内质网应激在糖尿病性心肌病心肌细胞凋亡中的作用及分子机制

项目编号： No.81200175

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 戴红艳

作者单位： 青岛市市立医院

项目金额： 23万元

中文摘要： 心肌细胞凋亡是糖尿病性心肌病的主要病理改变，也是促进糖尿病心功能障碍的重要机制。尾加压素Ⅱ(urotensin Ⅱ, UⅡ)作为最强缩血管物质，在我们的研究中被证实高表达于糖尿病心肌组织。我们的研究还发现，内质网应激（endoplasmic reticulum stress，ERS）诱导的心肌细胞凋亡在糖尿病性心肌病中明显增加。本项目综合国内外研究现状，提出UⅡ/氧化应激/ERS通路是糖尿病心肌病重要分子机制的假说。本项目拟进一步研究：①体外培养心肌细胞，探讨氧化应激在UⅡ诱导心肌细胞ERS及凋亡中的作用；探讨UⅡ/氧化应激/ERS在高糖、高游离脂肪酸诱导心肌细胞凋亡中的作用；②以1型、2型糖尿病心肌病大鼠模型为研究对象，研究RNAi抑制UⅡ后，大鼠心功能及心肌组织氧化应激、ERS及凋亡的变化。研究结果将为阐明糖尿病心肌病的发生机制提供新的理论依据，为糖尿病心肌病的干预提供潜在靶点。

中文关键词： 尾加压素Ⅱ；糖尿病心肌病；氧化应激；内质网应激；凋亡

英文摘要： Cardiomyocyte apoptosis is the major pathological change of diabetic cardiomyopathy, and also serves as the most important pathophysiological mechanism for diabetic cardiac dysfunction. Urotensin Ⅱ (UⅡ), currently known as the most powerful vasoconstrictor substances, has shown high expression level in diabetic myocardial tissue in our previous studies. It was also found that the endoplasmic reticulum stress (ERS)-induced cardiac myocyte apoptosis significantly increased in diabetic cardiomyopathy. Combined with the results from other research, we presumed that the UⅡ/oxidative stress(OS)/ERS pathway plays an important way in diabetic cardiomyopathy. This study will focus on the following area: ①The involvement of OS in the UⅡ-induced ERS and apoptosis in cultured cardiac myocyte. ②The role of UⅡ / OS / ERS pathway in diabetic metabolic abnormalities (high sugar, high free fatty acid)-induced cardiac myocyte apoptosis. ③The changes of cardiac function and myocardial tissue express of OS, the ERS and apoptosis after RNAi inhibition of UⅡ expression based on rats with type1 and type 2 diabetic cardiomyopathy, and the exploration of the role and molecular mechanisms of UⅡ in different types of diabetic cardiomyopathy. The results will help us to clarify the mechanism of diabetic cardiomyopathy, and will provide po

英文关键词： urotensin Ⅱ；Diabetic cardiomyopathy；oxidative stress；endoplasmic reticulum stress；apoptosis