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
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,Western blot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。
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abstractsObjective To investigate the alterations of mTOR signaling pathway and autophagy in the development of type 2 diabetes and early diabetic cardiomyopathy and to study their roles in pathogenesis of diabetic myocardium.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, Beclin-1 and LC3-Ⅱexpression in myocardium were determined by Western blot and immunohistochemistry.Results Compared with the control group, the expression of mTOR, p-mTOR, S6K1, Beclin-1 and LC3-Ⅱ level increased significantly in the experiment group of 2 weeks.The expression of p-mTOR 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.
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