Celastrol Reduces Hcy-induced Vascular Endothelial Injury By Regulating Sirt1/mTOR Pathway

BackgroundHomocysteine(Hcy)is closely related to the occurrence and development of cardiovascular diseases.Hcy produces excessive amounts of reactive oxygen species during metabolism and causes inflammation,which promote increased apoptosis,which in turn damages the vascular endothelium and leads to endothelial dysfunction.Sirt1 can effectively improve endothelial function and reduce oxidative stress and inflammation.The mammalian target of rapamycin(m TOR)can cause an increase in oxidative stress,increase endothelial cell apoptosis and autophagy,and cause vascular endothelial damage.The plant-derived celastrol has anti-inflammatory and antioxidant properties.This study mainly explores the protective effect of celastrol on Hcy-mediated endothelial injury through the Sirt1/mTOR pathway,which may provide a new target for the treatment of Hcy-induced vascular injury.ObjectiveTo investigate the apoptosis,expression of Sirt1 and m TOR after the intervention of celastrol in the human umbilical vein endothelial cells(HUVECs)injury model induced by high Hcy,and to clarify that celastrol has a protective effect on Hcy-induced endothelial damage and its related mechanism,in order to provide a new theoretical basis for traditional Chinese medicine to prevent and treat atherosclerosis.Methods1.Culture HUVECs in vitro.Use different concentration gradients of Hcy to treat HUVECs and establish a cell damage model.2.Then the cells were divided into three groups,first is control group,second is Hcy treatment group,last is Hcy+ Cel group.3.Detect cell apoptosis rate by flow cytometry;MTT method to detect cell viability in each group;Western Blot to detect the expression of Sirt1,m TOR,caspase-3,Bax protein in each group.Results1.Hcy inhibits the growth of HUVECs in a concentration-dependent manner.2.Celastrol can alleviate the decline of endothelial cell viability induced by Hcy.3.Celastrol can inhibit the activation of NADPH oxidase induced by Hcy.4.Celastrol can inhibit the activation of Bax and Cleaved-Caspase3 of endothelial cells induced by Hcy.5.Sirt1/mTOR pathway is involved in the protection of endothelial cells by Celastrol.ConclusionCelastrol reduces oxidative stress and cell apoptosis through the Sirt1/mTOR pathway,thereby delaying Hcy-mediated endothelial damage.