达格列净抑制血管紧张素Ⅱ诱导的心肌细胞肥大和凋亡  

Dapagliflozin inhibits angiotensinⅡ-induced cardiomyocyte hypertrophy and apoptosis

作　　者：邵双印[1] 蔡欣桐 肖莉丽[2] 高路[2] SHAO Shuangyin;CAI Xintong;XIAO Lili;GAO Lu(Department of Cardiac Surgery,He'nan Thoracic Hospital,Zhengzhou 450008,China;不详)

机构地区：[1]河南省胸科医院心外科,郑州450008 [2]郑州大学第一附属医院心血管内科,郑州450052

出　　处：《实用医学杂志》2024年第11期1526-1530,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81970201)。

摘　　要：目的探讨达格列净对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大反应和凋亡的影响。方法分离培养原代大鼠乳鼠心肌细胞,将其随机分为4组:对照组,AngⅡ组、达格列净1组(0.5μmol/L),达格列净2组(2μmol/L)。采用α-actin染色检测细胞面积,采用qPCR检测胚胎基因的转录,采用Tunel染色检测细胞凋亡水平,采用caspase3试剂盒检测caspase3活性,采用免疫印迹检测经典信号分子。结果AngⅡ组细胞面积明显大于对照组(P<0.05);达格列净1组、达格列净2组细胞面积低于AngⅡ组(P<0.05)。qPCR结果显示AngⅡ组胚胎基因转录明显高于对照组(P<0.05);达格列净1组,达格列净2组胚胎基因转录低于AngⅡ组(P<0.05)。tunel染色结果显示:AngⅡ组细胞凋亡数量高于对照组(P<0.05);达格列净1组,达格列净2组细胞凋亡数量低于AngⅡ组(P<0.05)。AngⅡ组细胞caspase3活性高于对照组(P<0.05);达格列净1组,达格列净2组细胞caspase3活性低于AngⅡ组(P<0.05)。免疫印迹检测结果显示AngⅡ组细胞胰岛素样生长因子1受体(IGF1R)和Akt激活程度低于对照组(P<0.05);达格列净1组,达格列净2组细胞IGF1R和Akt激活高于AngⅡ组(P<0.05)。结论达格列净可直接作用于心肌细胞,保护其免受AngⅡ诱导的损伤。Objective This study aimed to investigate the effect of Dapagliflozin on the hypertrophy and apoptosis of cardiomyocytes induced by angiotensin Ⅱ(Ang Ⅱ).Methods Primary rat neonatal cardiomyocytes were isolated,cultured and randomly divided into 4 groups:control group,Ang Ⅱ group,dapagliflozin group 1(0.5μmol/L),and dapagliflozin group 2(2μmol/L).α-actin staining was used to detect cell area.qPCR was applied to detect embryonic gene transcription.Tunel staining was adopted to detect cell apoptosis level.The caspase3 kit was used to detect caspase3 activityand western blotting was used to detect classical signal molecules.Results The cell surface area of the Ang Ⅱ group was significantly larger than that of the control group(P<0.05).The cell surface area of the dapagliflozin group 1 and the dapagliflozin group 2 was significantly lower than that of the Ang Ⅱ group(P<0.05).The results of qPCR showed that the fetal gene transcription of Ang Ⅱ group was significantly higher than that of the control group(P<0.05);the fetal gene transcription of dapagliflozin group 1 and dapagliflozin group 2 was lower than that of Ang Ⅱ group(P<0.05).Tunel staining showed that the number of apoptosis in the Ang Ⅱ group was higher than that in the control group(P<0.05);the number of apoptosis in the dapagliflozin group 1 and the Dapagliflozin group 2 was lower than that in the Ang Ⅱ group(P<0.05).The caspase3 activity of the cells in the Ang Ⅱ group was higher than that of the control group(P<0.05)but lower in dapagliflozin group 1 and the dapagliflozin group 2(P<0.05).The results of Western blotting showed that the activation of insulin-like growth factor 1 receptor(IGF1R)and Akt in the Ang Ⅱ group was lower than that in the control group(P<0.05)but increased in the dapagliflozin group 1 and 2 cells(P<0.05).Conclusion Dapagliflozin could directly act on cardiomyocytes to protect them from Ang Ⅱ-induced damage.

关 键 词：达格列净 SGLT2抑制剂 血管紧张素Ⅱ 心肌细胞 胰岛素样生长因子1受体 

分 类 号：R542.2[医药卫生—心血管疾病]