Resveratrol Alleviates Vascular Endothelial Damage Caused by Lower-Extremity Ischemia Reperfusion (I/R) through Regulating Keap1/Nrf2 Signaling-Mediated Oxidative Stress

The present study aims to investigate the protective effects of Resveratrol (RSV) against vascular endothelial damage caused by lower-extremity I/R and the underlying preliminary mechanism. The in vitro hypoxia reoxygenation (HR) model was established on HUVECs. Lower-extremity I/R model was established on rats followed by being treated with RSV and the pathological state of artery was evaluated by HE and EVG staining, while the apoptotic state of artery was detected by TUNEL assay. The cell viability was detected by MTT assay and the apoptotic state of cells was determined by Hoechst test and flow cytometry assay. DCFH-DA staining was used to measure the level of ROS and the production of MDA and SOD was measured by commercial kits. The expression level of Nrf2, Keap1, HO-1, Bcl-2, Bax, and Caspase-3 in cells was determined by Western blot. Nrf2 was knocked down by siRNA technology. Overall, our data indicated that increased cell viability, declined apoptotic rate, and alleviated oxidative stress were observed in RSV treated HR HUVECs, which were significantly reversed by knocking down Nrf2. Animal experiment revealed that the pathological and apoptotic state of femoral artery were dramatically ameliorated by the treatment of RSV, accompanied by the alleviated oxidative stress, which were abolished by the co-administration of ML385, an inhibitor of Nrf2. Taken together, our data revealed that RSV might alleviate vascular endothelial injury induced by lower-extremity I/R injury through regulating Keap1/Nrf2 signaling-mediated oxidative stress.