AIM: To explore the effect of dapagliflozin on the apoptosis and oxidative stress of high glucose-induced human retinal vascular endothelial cells and its regulatory effect on forkhead FOXO4.

METHODS: High glucose-induced human retinal vascular endothelial cells(HRVECs)were used to establish a cell injury model(high glucose group). Experimental groups include high glucose+dapagliflozin low-dose group(1ng/L dapagliflozin), high glucose+dapagliflozin medium-dose group(5ng/L dapagliflozin), high glucose+dapagliflozin high-dose group(10ng/L dapagliflozin), high glucose+dapagliflozin high-dose+pcDNA group, high glucose+dapagliflozin high-dose+pcDNA-FOXO4 group, and normal sugar group(5.5mmol/L D-glucose). Flow cytometry was used to detect the apoptosis rate. The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)were tested with corresponding kits. Western blot assay was used to detect the protein level of FOXO4.

RESULTS: Compared with the normal sugar group, the apoptosis rate(P<0.05), the level of MDA(P<0.05)and FOXO4(P<0.05)were increased, but the level of SOD was decreased(P<0.05)in high-glucose group. Compared with the high glucose group, cell apoptosis rate(P<0.05), the level of MDA(P<0.05)and the protein level of FOXO4 were decreased(P<0.05), but the level of SOD was increased(P<0.05)in high glucose+medium-dose dapagliflozin group and high glucose+high-dose dapagliflozin group. Compared with high glucose+dapagliflozin high-dose+pcDNA group, the apoptosis rate(P<0.05)and the level of MDA(P<0.05)were increased, but the level of SOD was decreased(P<0.05)in high glucose+dapagliflozin high-dose+pcDNA-FOXO4 group(P<0.05).

CONCLUSION: Dapagliflozin could inhibit oxidative stress and cell apoptosis in high glucose-induced HRVECs by down-regulating FOXO4, thereby reducing cell damage.