Protective Effects Of Curcumin On Vascular Endothelial And Endothelial Progenitor Cells In Atherosclerotic Rats And Its Mechanisms

Objective: To investigate the effect of curcumin on reversing vascular endothelial and endothelial progenitor cell injury in atherosclerotic rats,and to explore its mechanism.Methods:Thirty-two male SD rats were adaptively raised for 1 week,after that,they were randomly divided into 4 groups: the control group,the model group,the curcumin group and the curcumin+ZnPP? group.The latter three groups were fed with high fat diet along with liquid nitrogen frostbite of the right common carotid artery,intraperitoneal injection of vtamin D3,the immune damage in order to make atherosclerosis model.From the fourteenth week on,drug intervention was conducted for two weeks in the latter three groups,among which,curcumin group was given curcumin l00mg/kg.d by gavage,curcumin+ZnPP? group was administered curcumin 100mg/kg.d by gavage,followed by intraperitoneal injection of ZnPP? 7.5mg/kg for once every other day while model group was administered equal amount of normal saline.The control group was fed with normal diet and treated with the same methods as that of other three groups with normal saline instead of various drugs.The blood samples were taken to detect following indexes: the amount of circulating endothelial cells and endothelial progenitor cells;inflammation index: tumor necrosis factor(TNF-?)and interleukin-6(IL-6)level;oxidative stress index: malondialdehyde(MDA)level ? total antioxidant capacity(T-AOC);NO content.The right common carotid artery was used for histopathologic detection as well as immunohistochemical analysis for HO-1 protein expression.Endothelial progenitor cells in each group were isolated from peripheral blood and cultured in vitro to detect its proliferative and migratory activity,adhesion,NO secretion as well as HO-1 protein expression.Results:Compared with the control group,AS plaques formation in the carotid artery was obvious in model group,furthermore,there was significant increase in the serum levels of TNF?,IL-6 and MDA,the amount of circulating endothelial cells and endothelial progenitor cells in model group,while the T-AOC,the content of NO,proliferative and migratory activity,adhesion of EPCs decreased significantly(P<0.05 or P<0.01).Compared with the model group,the expression of HO-1 protein in the vessel and cultured EPCs in curcumin group increased markedly,the levels of serum TNF?,IL-6 and MDA,and the number of circulating endothelial cells drop significantly,and the contents of T-AOC and NO significantly rise(P<0.05 or P<0.01).In addition,the curcumin group also show higher number of EPCs,significant increased proliferative and migratory activity,adhesion and NO secetion of ECPs(P<0.01).Although the expression of HO-1 in the vessel and cultured EPCs also significantly increased in curcumin+ZnPP? group(P < 0.05),there was no significant alteration in serum TNF?,IL-6,T-AOC,MDA,NO content and circulating endothelial cell count compared to the model group(P > 0.05).Alikely,There was no significant improvement in the number and function of EPCs.Conclusion:1.There is marked increase in the level of inflammation and oxidative stress in AS rats,which caused vascular endothelial and EPCs injury.2.Curcumin could effectively inhibit the inflammatory and oxidative stress response in AS rats,which thus can relieve endothelial impairment,promote the mobilization of EPCs and enchance the function of EPCs.3.The protective effects of curcumin on vascular endothelial and EPCs were mainly mediated by inducing the expression of HO-1 protein.