Atorvastatin Inhibits High Glucose-induced Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells by SIRT1/NADPH Oxidase Pathway / 中国循环杂志

ABSTRACT

Objective: To explore the effect of atorvastatin (Atv) on high glucose-induced oxidative stress injury in human umbilical vein endothelial cells (HUVECs) by SIRT1/NADPH oxidase pathway with the possible mechanisms. Methods: HUVECs were cultured in low glucose medium and then divided into 6 experimental groups:①Normal group,②Osmotic pressure control group,③High glucose (HG) group,④HG+Atv (0.1, 1.0, 10.0)μmol/L group,⑤HG+sirtinol (SIRT1 inhibitor) group,⑥HG+apocynin (NOX4 inhibitor) group, and HUVECs were further cultured for 24 hours. The cell proliferation was examined by CCK-8 kit, ROS level was detected by lfow cytometry method, protein expressions of SIRT1 and NOX4 were measured by Western blot analysis. Results: ① Compared with Normal group, HG group had decreased HUVECs proliferation, Atv improved the HG inhibited proliferation in a does dependent manner. ② HG group had the higher level of ROS, increased NOX4 protein expression and decreased SIRT1 protein expression. ③ In HG condition, Atv up-regulated SIRT1 expression and down-regulated ROS and NOX4 expressions in a does dependent manner.④In HG condition, sirtinol decreased SIRT1 expression, increased NOX4 expression, and apocynin decreased NOX4 expression, while it had no inlfuence on SIRT1 expression. Conclusion: Atorvastatin could resist HG-induced oxidative stress injury in HUVECs, which might be related to up-regulated SIRT1 expression, and SIRTI plays the role in NADPH oxidase at upstream.