摘要
Abstract
Objective:To investigate the effect of andrographolide(AP)on vascular endothelial inflammation and high mobility group box 1(HMGB1)/receptor of advanced glycation end product(RAGE)signaling pathway in rats with thrombosis angiitis obliterans(TAO).Methods:A TAO rat model was established and the successfully modeled rats were randomly divided into a model group(TAO group),low-dose and high-dose andrographolide groups(AP-L and AP-H groups),and high-dose andrographolide+pathway activator group(AP-H+rHMGB1 group),with 12 rats in each group.Another 12 healthy rats served as the control group(Control group).The TAO lesions of rats in each group were graded and scored.Blood viscometer was used to measure whole blood and plasma viscosity.ELISA was utilized to detect levels of thrombotic factors.H-E staining was applied to observe the pathological morphology of femoral artery tissue.Western blotting was employed to detect the protein expression related to vascular endothelial inflammation and HMGB1/RAGE signaling pathway.Results:Compared with the Control group,the TAO group exhibited more severe shedding of endothelial cells in the femoral artery tissue,with a large amount of thrombus formation.The whole blood viscosity,plasma viscosity,thromboxane B2(TXB2)levels,and expressions of IL-6,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),HMGB1,RAGE,and p-NF-κB p65/NF-κB p65 elevated,while the 6-Keto-prostaglandin F1α(6-Keto-PGF1α)level decreased.Compared with the TAO group,the AP-L and AP-H groups showed reduced shedding of endothelial cells and mild thrombosis in the femoral artery tissue,with decreased whole blood viscosity,plasma viscosity,TXB2 level,and IL-6,ICAM-1,VCAM-1,HMGB1,RAGE,and p-NF-κB p65/NF-κB p65 expression,and increased 6-Keto-PGF1α level.Compared with the AP-H group,the AP-H+rHMGB1 group exhibited worsened shedding of endothelial cells and increased thrombosis in femoral arterial tissue,with elevated whole blood viscosity,and plasma viscosity.The TXB2 level and and expression of IL-6,ICAM-1,VCAM-1,HMGB1,RAGE,and p-NF-κB p65/NF-κB p65 increased,while the 6-Keto-PGF1α level decreased.Conclusion:Andrographolide can alleviate vascular endothelial inflammation in TAO rats,and its mechanism may be associated with the inhibition of the HMGB1/RAGE signaling pathway.关键词
穿心莲内酯/高迁移率族蛋白1/晚期糖基化终末产物受体/血栓闭塞性脉管炎/血管内皮/炎症Key words
andrographolide/high mobility group box 1/receptor of advanced glycation end product/thrombo angiitis obliterans/vascular endothelium/inflammation分类
医药卫生
