Protective effect of dapagliflozin on renal tubular epithelial cells in diabetic nephropathy and its related mechanism / 中华内分泌外科杂志

ABSTRACT

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.