尿石素A对糖尿病小鼠心肌细胞自噬的影响  

Effect of urolithin A on autophagy of myocardial cells in diabetic mice

作　　者：朱小艳 周友 岑慧裕 黄雅焱 高智敏 吴晓倩 ZHU Xiao-yan;ZHOU You;CEN Hui-yu;HUANG Ya-yan;GAO Zhi-min;WU Xiao-qian(Dept of Pharmacology, Guangzhou Medical University, Guangzhou 511436,China)

机构地区：[1]广州医科大学药学院药理学教研室,广东广州511436

出　　处：《中国药理学通报》2019年第6期810-815,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81573429);广东省自然科学基金资助项目(No 2015A030313476);广东省教育厅高等学校优秀青年教师培养计划(No Yq2013134);广州市科技计划项目科学研究专项(No 2015215)

摘　　要：目的探讨尿石素A(urolithin A,UA)对糖尿病小鼠心肌细胞自噬的影响。方法葡萄糖(5. 5、20、33、47 mmol·L^(-1))及不同浓度的UA刺激乳鼠心肌细胞48 h,MTT比色法检测细胞存活率,Western blot法检测细胞内自噬蛋白LC3、p62的表达水平。健康♂C57BL/6小鼠连续6 d腹腔注射链脲佐菌素(streptozotocin,STZ)制备糖尿病小鼠模型,灌胃给予UA连续治疗10周,超声检测心功能指标,Masson染色观察心肌病理切片。结果 33 mmol·L^(-1)高糖刺激心肌细胞48 h后,细胞存活率下降,自噬蛋白p62、LC3Ⅱ、LC3Ⅱ/Ⅰ比值增加(P <0. 05),给予UA后,上述蛋白表达水平下降。与正常组比较,糖尿病组心功能显示E/A峰比值下降(P <0. 05),Masson结果显示胶原纤维的表达升高,UA干预后E/A峰比值增加(P <0. 05),心肌胶原纤维的表达降低。结论 UA可通过影响心肌细胞内自噬,发挥保护糖尿病心肌病的作用。Aim To explore the effect of urolithin A(UA) on autophagy of cardiomyocytes in diabetic mice. Methods Glucose(5.5, 20, 33, 47 mmol·L -1 ) and UA at different concentrations were used to stimulate the neonatal rat cardiomyocytes for 48 h. MTT assay was used to detect the survival rate of cardiomyocytes. Western blot was used to detect the expression of autophagy proteins LC3 and p62. Healthy male C57BL/6 mice were intraperitoneally injected with STZ for 6 days to establish diabetic mouse model. UA was given by intragastric administration for 10 weeks and the cardiac function indicators were detected by ultrasound. Masson staining was used to observe the myocardial pathological sections. Results After treatment with 33 mmol·L -1 of high glucose for 48 h, the survival rate of cardiomyocytes decreased, and autophagy protein p62, LC3 Ⅱ, the ratio of LC3 Ⅱ/Ⅰ increased, which were reduced with UA treatment. Compared with the control mice, the cardiac function of diabetic cardiomyopathy mice showed decreased ratio of E/A peak. Masson showed that cardiac fibrosis expression decreased after UA administration. Conclusion UA can protect diabetic cardiomyopathy by affecting myocardial autophagy.

关 键 词：糖尿病心肌病 自噬 尿石素A 高糖 P62 LC3 

分 类 号：R-332[医药卫生] R284.1