Astragaloside ? Improves Vascular Endothelial Dysfunction By Inhibiting The TLR4/NF-?B Signaling Pathway

The aim of this study was to investigate the protective effect and mechanism of As-? on vascular endothelial dysfunction in STZ induced SD diabetic rats.Methods In vivo,a single intraperitoneal injection of streptozotocin(STZ,65 mg/kg)was used to establish diabetic model.Rat tail vein blood glucose level above 16.7 mmol/L were regarded as a criterion for successful establishment of diabetic model.After successful establishment of a diabetic rat model,As-?(40 and 80 mg/kg/d)was orally administered to rats for 8 weeks.The rats were randomly divided into four groups: Normal,Diabetic group,As-? 40 mg/kg group,and As-? 80 mg/kg group.In vitro,human umbilical vein endothelial cells(HUVECs)were treated with high glucose(33 m M glucose)in the presence or absence of As-?,BAY 11-7082(NF-?B p65 inhibitor),TAK-242(TLR4 inhibitor)and L-NAME(NO synthesis inhibitor)+ As-?.Endothelial function in isolated aortic rings was examined;serum interleukin-6(IL-6)and tumor necrosis factor-?(TNF-?)were tested by ELISA.The expression of nuclear Factor-?B p65(NF-?B p65)in aortic tissue was detected by immunohistochemistry.Plasma nitric oxide(NO)was measured by the nitrate reductase method.The expressions of endothelial nitric oxide synthase(e NOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and toll-like receptor 4(TLR4)in aortic tissue were determined by western blot.Results The results showed that As-? significantly improved aortic endothelial function;increased e NOS expression and NO production;and decreased the content of IL-6 and TNF-? and the expressions of VCAM-1,ICAM-1,TLR4,and nuclear NF-?B p65 in vitro and in vivo.In addition,the above mentioned effects of As-? on human umbilical vein endothelial cells(HUVECs)were similar to that of TAK-242(TLR4 inhibitor)and Bay 11-7082(NF-?B p65 inhibitor).Furthermore,L-NAME(NO synthesis inhibitor)partially abolished the effect of As-?.Conclusions As-? has a protective effect on vascular endothelial dysfunction induced by hyperglycemia,which may be mediated partly through TLR4/NF-?B signaling pathway.These findings provide a theoretical basis for further study of As-? in the treatment of diabetes-related endothelial dysfunction.