银杏叶提取物激活Nrf2/ARE通路改善慢性间歇性低氧诱导大鼠血管内皮功能障碍  

Ginkgo biloba extract activates Nrf2/ARE pathway to improve vascular endothelial dysfunction induced by chronic intermittent hypoxia in rats

作　　者：司胜勇 李虹漫 缪思斯 韩肖 李治菁 韦朝俊 刘大男 SI Sheng-yong;LI Hong-man;MIAO Si-si;HAN Xiao;LI Zhi-jing;WEI Chao-jun;LIU Da-nan(Dept of Hypertension,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学附属医院高血压科,贵州贵阳550004

出　　处：《中国药理学通报》2024年第10期1837-1844,共8页Chinese Pharmacological Bulletin

基　　金：贵州省卫健委科学技术基金资助项目(No gzwkj2021-003)。

摘　　要：目的探讨银杏叶提取物(Ginkgo biloba extract,GBE)对慢性间歇性低氧(chronic intermittent hypoxia,CIH)诱导大鼠血管内皮功能障碍的影响及相关机制。方法构建CIH大鼠模型,并用50、100 mg·kg^(-1)的GBE灌胃,检测各组大鼠尾动脉收缩压(systolic blood pressure,SBP);HE染色检测主动脉组织形态;DAF-FM DA染色和硝酸还原酶法检测NO水平;ELISA法检测血清ET-1、TNF-α、IL-6水平;DHE染色检测主动脉组织活性氧水平;试剂盒检测血清MDA、SOD、GSH-Px水平;Western blot检测主动脉组织VCAM-1、ICAM-1、细胞核Nrf2、HO-1、NQO1水平。结果GBE明显降低CIH大鼠的尾动脉SBP、ET-1、活性氧、MDA、VCAM-1、ICAM-1、TNF-α、IL-6水平,明显增加NO、SOD、GSH-Px、细胞核Nrf2、HO-1、NQO1水平。GBE明显改善CIH大鼠主动脉组织形态学。结论GBE可改善CIH模型大鼠血管内皮功能障碍,降低血压,其机制可能与激活Nrf2/ARE通路、抑制氧化应激与炎症反应有关。Aim To investigate the effects of Ginkgo biloba extract(GBE)on vascular endothelial dysfunc-tion induced by chronic intermittent hypoxia(CIH)in rats and its related mechanisms.Methods The CIH rat model was established,and 50 and 100 mg·kg^(-1) GBE was administered by intragastric administration.The systolic blood pressure(SBP)of the tail artery was detected in each group.HE staining was used to detect the morphology of aorta tissue.DAF-FM DA staining and nitric reductase assay were used to detect NO levels.ELISA was used to detect serum ET-1,TNF-αand IL-6 levels.DHE staining was used to detect reactive oxygen species(ROS)levels of aortic tissue.Kits were used to detect the serum levels of MDA,SOD and GSH-Px.Western blot was used to detect the levels of VCAM-1,ICAM-1,nucleus Nrf2,HO-1 and NQO1 of aortic tissue.Results GBE significantly decreased the levels of SBP,ET-1,ROS,MDA,VCAM-1,ICAM-1,TNF-αand IL-6,and significantly increased the levels of NO,SOD,GSH-Px,nuclear Nrf2,HO-1 and NQO1 in CIH rats.GBE significantly improved the histomorphology of aorta in CIH rats.Conclusions GBE can improve vascular endothelial dysfunction and reduce blood pressure in CIH model rats.The mechanism may be related to the activation of Nrf2/ARE pathway and the inhibition of oxidative stress and inflammation by GBE.

关 键 词：银杏叶提取物 Nrf2/ARE通路 慢性间歇性低氧 血管内皮功能障碍 高血压 氧化应激 

分 类 号：R-332[医药卫生] R284.1R322.121R349.1R544.1R852.15