南方医科大学学报2018，Vol.38Issue(5)：520-526,7.
Exendin-4通过调控Sirt1/PGC1α延缓糖尿病小鼠心肌损伤
Exendin-4 alleviates diabetic cardiomyopathy in mice by regulating Sirt1/PGC1α
摘要
Abstract
Objective To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism. Methods C57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks,respectively.The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC.The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice. Results Compared with the normal control mice,the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels(P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice. Conclusions Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.关键词
exendin-4/糖尿病心肌病/Sirt1/PGC1α/氧化应激/线粒体功能Key words
exendin-4/diabetic cardiomyopathy/Sirt1/PGC1α/oxidative stress/mitochondrial function引用本文复制引用
蔡迎迎,邹少洲,范存霞,吴春艳,方舒,李萍,薛耀明,关美萍..Exendin-4通过调控Sirt1/PGC1α延缓糖尿病小鼠心肌损伤[J].南方医科大学学报,2018,38(5):520-526,7.基金项目
国家自然科学基金(81628004,31400992,81470047) （81628004,31400992,81470047）
广东省科技计划社会发展项目(2013B022000061) （2013B022000061）
吴阶平医学基金会临床科研专项(320.6750.15198)Supported by National Natural Science Foundation of China(81628004,31400992,81470047). （320.6750.15198）
