2型糖尿病大鼠早期心肌病mTOR信号通路的改变与自噬损伤  

Alterations of mTOR pathway and autophagy in early type 2 diabetic cardiomyopathy in rats

作　　者：孙晓慧[1,2] 尹茂山 牟艳玲[2] 

机构地区：[1]济南大学山东省医学科学院医学与生命科学,250200 [2]山东省医学科学院药物研究所

出　　处：《中华病理学杂志》2016年第10期707-710,共4页Chinese Journal of Pathology

基　　金：国家自然科学基金（30701022）;山东省优秀中青年科学家科研奖励基金计划（BS2013SW008）

摘　　要：目的检测哺乳动物雷帕霉素靶蛋白（mTOR）信号通路及自噬相关蛋白在糖尿病大鼠心肌早期损伤中的表达变化，探讨其在糖尿病心肌病发生发展中的作用。方法sD大鼠30只经高脂饮食5周后，腹腔注射链脲佐菌素建立2型糖尿病大鼠模型，实验将大鼠分为空白对照组和糖尿病2周、4周模型组，Westernblot和免疫组织化学检测心肌mTOR、p-mTOR、S6K1、Beclin-1和LC3-Ⅱ蛋白表达变化。结果糖尿病2周模型组大鼠相对于正常对照组心肌mTOR、p-mTOR、S6K1、Beclin-1和LC3-Ⅱ表达显著增加，p-mTOR及S6K1表达4周模型组比2周模型组增加更明显。结论mTOR信号通路可能通过调控心肌自噬损伤，参与早期糖尿病心肌病的发生发展。Objective To investigate the alterations of mTOR signaling pathway and autophagy in the development of type 2 diabetes and early diabetic eardiomyopathy and to study their roles in pathogenesis of diabetic myoeardium. Methods A type 2 diabetes rat model was established by injection of streptozocin after five-week of high fat diet. The rats were randomly divided into control group, experiment group of 2 weeks and experiment group of 4 weeks. Alterations of mTOR, p-mTOR, S6K1, Beelin-1 and LC3-Ⅱ expression in myoeardium were determined by Western blot and immunohistoehemistry. Results Compared with the control group, the expression of mTOR, p-mTOR, S6K1, Beclin-1 and LC3-U level increased significantly in the experiment group of 2 weeks. The expression of p-roTOR and S6K1 increased significantly in the experiment group of 4 weeks compared with those of the experiment group of 2 weeks. Conclusions mTOR signaling pathway is activated in early diabetic myocardial injury via autophagy. The findings may provide a new therapeutic target for diabetic cardiomyopathy.

关 键 词：糖尿病 2型 糖尿病心肌病 自噬 MTOR信号通路 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]