黄芪甲苷通过HIF-1α/iNOS通路对下肢深静脉血栓大鼠血管内皮功能的影响及机制研究  

Effect and mechanism of astragaloside on vascular endothelial function in rats with deep venous thrombosis of lower extremity through HIF-1α/iNOS Signaling Pathway

作　　者：朱俊 黄之龙 ZHU Jun(Affiliated Lu’an Hospital(Lu’an People’s Hospital)to Anhui Medical University,Lu’an 237000,Anhui,China)

机构地区：[1]安徽医科大学附属六安医院(六安市人民医院)内科,安徽六安237000

出　　处：《牡丹江医学院学报》2024年第5期28-33,共6页Journal of Mudanjiang Medical University

摘　　要：目的研究黄芪甲苷对下肢深静脉血栓大鼠血管内皮功能的保护作用,并探讨其潜在作用机制。方法线栓法构建大鼠下肢深静脉血栓模型。将60只雄性SD大鼠随机分为假手术组、模型组、黄芪甲苷低、中、高剂量治疗组[20、40、80 mg/(kg·d)]和HIF-1α选择性激动剂组[20 mg/(kg·d)]。采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测IL-6、IL-1β、TNF-α、血栓素A2(thromboxane A2,TXA2)与前列环素(prostaglin 2,PGI2)水平;HE染色法观察大鼠下腔血脉血栓状态;TUNEL染色检测血管内皮细胞凋亡情况;Western Blot检测HIF-1α、iNOS、caspase 9、caspase 3蛋白表达。结果与假手术组相比,模型组IL-6、IL-1β、TNF-α、TXA2水平显著升高,PGI2水平显著降低;HE染色结果可见红色和混合血栓,血管壁伴炎性细胞浸润;血管内皮细胞凋亡数显著增加;HIF-1α、iNOS蛋白表达明显下调;caspase 9、caspase 3蛋白表达明显上调。与模型组相比,黄芪甲苷低、中、高剂量治疗组和HIF-1α选择性激动剂组IL-6、IL-1β、TNF-α、TXA2水平显著降低,PGI2水平显著升高;HE染色结果可见无血管内皮细胞掉落,仅有极少量炎性细胞浸润;血管内皮细胞凋亡数显著减少;HIF-1α、iNOS蛋白表达明显上调;caspase 9、caspase 3蛋白表达明显下调。结论黄芪甲苷对下肢深静脉血栓大鼠血管内皮功能具有明显的保护作用,其机制可能与调控HIF-1α/iNOS信号通路有关。Objective To investigate the protective effect of astragaloside on vascular endothelial function in rats with deep vein thrombosis of lower extremity and to explore its potential mechanism.Methods The rat model of lower extremity deep vein thrombosis was established.Sixty male SD rats were randomly divided into sham operation group,model group,astragaloside low,medium and high dose treatment group and HIF-1αselective agonist group.Enzyme linked immunosorbent assay(ELISA)was used to detect IL-6,IL-1β,TNF-α,thromboxane A2(TXA2)and Prostaglin 2(PGI2)level;The state of blood thrombus was observed by HE staining.TUNEL staining was used to detect apoptosis of vascular endothelial cells.The expression of HIF-1α,iNOS,caspase 9 and caspase 3 was detected by Western Blot.Results Compared with sham operation group,the levels of IL-6,IL-1β,TNF-αand TXA2 in model group were significantly increased,while the level of PGI2 was significantly decreased.HE staining showed red and mixed thrombus and the vessel wall was infiltrated by inflammatory cells.The number of apoptosis vascular endothelial cells increased significantly.The expressions of HIF-1αand iNOS were significantly downregulated.The expressions of caspase 9 and caspase 3 were significantly upregulated.Compared with model group,the levels of IL-6,IL-1β,TNF-αand TXA2 in Astragaloside low,medium and high dose treatment groups and HIF-1αselective agonist group were significantly decreased,while the level of PGI2 was significantly increased.HE staining showed no endothelial cell drop and only a small amount of inflammatory cells infiltrated.The number of apoptosis vascular endothelial cells decreased significantly.The expression of HIF-1αand iNOS was significantly upregulated.The expressions of caspase 9 and caspase 3 were significantly down-regulated.Conclusion Astragaloside has obvious protective effect on vascular endothelial function in rats with deep venous thrombosis of lower extremity,and the mechanism may be related to the regulation of HIF-1α/iNOS signa

关 键 词：黄芪甲苷 下肢深静脉血栓 内皮功能 HIF-1α/iNOS 

分 类 号：R543.6[医药卫生—心血管疾病]