Propofol activates autophagic activity of vascular endothelial cells by inhibiting SENP1 expression and attenuates vascular endothelial injury induced by ischemia-reperfusion in orthopedic surgery

Abstract

The aim of this study was to examine the effect and mechanism of SENP1 in the protection of vascular endothelial cells by propofol during ischemia-reperfusion (IR) injury. Thirty-eight patients undergoing minor lower limb orthopedic surgery under general anesthesia were included, and divided evenly into sevoflurane group and propofol group. Peripheral blood was collected before fixing tourniquets (T0 time point) and one hour after releasing tourniquets (T1 time point). Contents of endothelin, vWF and malondialdehyde were determined by enzyme-linked immunosorbent assay to evaluate vascular injury. Quantitative real-time polymerase chain reaction was used to determine mRNA expression; western blotting, to determine protein expression; CCK-8 assay, Transwell assay and flow cytometry, to examine the proliferation, migration and apoptosis of human umbilical vein endothelial cells (HUVECs); western blotting and laser scanning confocal microscopy, to analyze autophagy of HUVECs; protein immunoprecipitation, to examine the relationship between SENP1 and the SUMOylation of autophagy-associated VPS34 protein. The results showed that the contents of peripheral blood vessel injury markers and the expression of SENP1 were elevated when vascular injury was induced by IR in patients undergoing orthopedic surgery, whereas propofol reduced these levels. Inhibition of SENP1 expression reduced injury of HUVECs induced by IR. Silencing expression of SENP1 promoted autophagy of HUVECs. SENP1 promoted deSUMOylation of VPS34, leading to reduced autophagy of HUVECs. The study demonstrates that propofol activates autophagic activity of HUVECs by inhibiting SENP1 expression and attenuates vascular endothelial injury induced by IR in orthopedic surgery. This effect may be related to SENP1 regulating the deSUMOylation of VPS34.