达格列净对糖尿病肾病肾小管上皮细胞的保护作用及相关机制研究  

Protective effect of dapagliflozin on renal tubular epithelial cells in diabetic nephropathy and its related mechanism

作　　者：张爱鸣 刘香兰[2] Zhang Aiming;Liu Xianglan(Department of Endocrinology,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine,Wenzhou 325000,China;Department of Endocrinology,Quzhou People’s Hospital,Quzhou 324000,China)

机构地区：[1]浙江省温州市中西医结合医院内分泌科,温州325000 [2]浙江省衢州市人民医院内分泌科,衢州324000

出　　处：《中华内分泌外科杂志》2021年第3期230-233,共4页Chinese Journal of Endocrine Surgery

基　　金：衢州市科技局课题项目(2015N1009795)。

摘　　要：目的探讨达格列净对高糖诱导的HK-2细胞损伤的影响。方法将HK-2细胞分成4组:正常对照组(negative control,NC)、高糖模型组(high glucose group,HG)、达格列净组(dapagliflozin,CS-179)和阳性对照二甲双胍组(positive control,PC)。给药作用24 h后,通过CCK-8法检测细胞存活率;通过多功能酶标仪测定ROS、SOD、CAT活力和MDA含量;Western blot法检测Nrf2蛋白的表达情况。结果CCK8结果显示,高糖模型组细胞存活率为58.0%±0.8%,达格列净组为87.0%±0.4%,达格列净能明显提高HK-2细胞存活率,差异有统计学意义(P<0.01)。酶标仪检测发现,与高糖模型组对比(ROS:3.46±0.05,MDA:25.37±0.61,SOD:55.89±4.09,CAT:10.22±1.67),达格列净能降低高糖导致的ROS(1.97±0.04)和MDA(9.5±0.4)的蓄积(均P<0.01),提高SOD(114.95±4.19)和CAT(32.83±2.01)的活力(均P<0.01);与高糖模型组中Nrf2蛋白表达量(0.26±0.03)对比发现,达格列净组中Nrf2蛋白(0.48±0.03)的表达明显升高(P<0.01)。结论达格列净可改善高糖诱导的HK-2细胞损伤,其作用机制可能是通过降低HK-2细胞氧化损伤,激活Nrf2来发挥保护作用的。Objective To investigate the protective effect of dapagliflozin on cell damage and in HK-2 cells induced by high concentration of glucose.Methods HK-2 cells were divided into four groups:control group(NC),high glucose model group(HG),dapagliflozin group(CS-179)and metformin group(PC).After treatment with different drugs for 24 h,CCK-8 assay was applied to determine HK-2 cells viability;ROS,SOD,CAT and MDA levels were measured by a multi-detection reader;The protein expression of Nrf2 was determined by Western blot.Results The results of CCK8 showed that the cell survival rate of the high glucose model group was 58.0%±0.8%,and that of the dapagliflozin group was 87.0%±0.4%.Dapagliflozin significantly increased the survival rate of HK-2 cells,and the results were statistically significant(P<0.01).The microplate reader test found that compared with the high glucose model group(ROS:3.46±0.05,MDA:25.37±0.61,SOD:55.89±4.09,CAT:10.22±1.67),dapagliflozin reduced the accumulation of ROS(1.97±0.04)and MDA(9.5±0.4)caused by high glucose in HK-2 cells(both P<0.01),increasing the vigor of SOD(114.95±4.19)and CAT(32.83±2.01)(both P<0.01).Compared with the expression of Nrf2 protein in the high glucose model group(0.26±0.03),the expression of Nrf2 protein(0.48±0.03)in dapagliflozin group was significantly increased(P<0.01).Conclusion Dapagliflozin can alleviate the HK-2 cells damage induced by high concentration of glucose via reducing oxidative damage,and acti-vating Nrf2 antioxidant transcription factor.

关 键 词：达格列净 HK-2 氧化应激 糖尿病肾病 Nrf2转录因子 

分 类 号：R587.1[医药卫生—内分泌]