The Mechanism Of Resveratrol In Delaying Oxidative Stress-induced Aging Of Myocardial And Endothelial Cells

PurposeOxidative stress can induce cell aging,which is a new risk factor of cardiovascular disease.The protective effect of resveratrol on cardiovascular system has been confirmed,but the mechanism is not clear.Resveratrol is a SIRT1 promoter,and PGC-1α is an important coactivator.The mechanism of action of resveratrol and PGC-1α in oxidative stress of endothelial cells and their relationship with p53/p21,an aging related protein,need further study.Therefore,this study investigated the relationship between autophagy induced by resveratrol SIRT1/PGC-1α and cell oxidative stress and aging by oxidative stress and resveratrol intervention.Materials and methods1.KM mice were divided into normal group(NC),D-galactose group(D-gal),low,medium and high dose resveratrol+D-galactose group(L-RESV),(M-RESV),(H-RESV))The levels of superoxide dismutase(SOD),malondialdehyde(MDA),indexes SIRT1,PGC-1α,LC3 and p62Results:1.Compared with the D-gal group,the RESV group can reduce the content of MDA and serum LDH and CKMB in the myocardial tissue of the mouse,and increase the content of SOD in the myocardial tissue(P<0.05).(P<0.05),in which the effect of M-RESV group was obvious.2.Hydrogen peroxide can induce the up-regulation of cell senescence-related proteins p53 and p21 and cell autophagy negative related protein p62.In senescent cells,different concentrations of resveratrol can down-regulate the expression of p53 and p21 proteins(p<0.05),and also up-regulate the ratio of LC3 II/I to promote the degradation of p62 protein(p<0.05),of which 10 μmol/L resveratrol has obvious effect.3.10 μmol/L resveratrol intervention,after oxidative stress,endothelial cell LC3 protein increased,p62 protein decreased,SOD increased,ROS,MDA and ET-1 content decreased,endothelial function NO production increased,suggesting white content Alcohol can enhance the autophagy ability of senescent cells and reduce oxidative stress.When 3-MA is added,this effect of resveratrol is inhibited.4.10 μmol/L resveratrol can increase the expression of SIRT1,PGC-la protein(p<0.05),3 down-regulate the amount of p53 and p21 protein.After adding SIRT1 inhibitor EX527,SIRT1,PGC-la,LC3 protein expression and p62 protein decomposition were significantly inhibited(p<0.05),and p53 and p21 protein expression levels increased(p<0.05).Conclusion:1.Oxidative stress can increase the expression of p53 and p21 proteins in mouse myocardial tissue and umbilical vein endothelial cells.Resveratrol can reduce oxidative stress by increasing the autophagy and reduce P53 and p21 proteins,and delay the aging of tissue cells.2.Under oxidative stress,low concentration of resveratrol promotes autophagy of inhibitor EX527,SIRT1,PGC-1α,LC3 protein expression and p62 protein decomposition were significantly inhibited(p<0.05),and p53 and p21 protein expression levels increased(p<0.05).Conclusion:1.Oxidative stress can increase the expression of p53 and p21 proteins in mouse myocardial tissue and umbilical vein endothelial cells.Resveratrol can reduce oxidative stress by increasing the autophagy and reduce P53 and p21 proteins,and delay the aging of tissue cells.2.Under oxidative stress,low concentration of resveratrol promotes autophagy of myocardial tissues and endothelial cells and delays aging;high concentration of resveratrol plays an inhibitory role.3.Resveratrol can promote cell autophagy by up-regulating the level of Sirtl/PGC-1α and down-regulate the p53/p21 pathway to improve hydrogen peroxide-induced senescence of umbilical vein endothelial cells.