五味子甲素改善氧化应激引起的内皮功能障碍  

SchA ameliorates endothelial dysfunction caused by oxidative stress

作　　者：侯惠民 张文文 赵卫萍 赵鑫 朴贤美 HOU Hui-min;ZHANG Wen-wen;ZHAO Wei-ping;ZHAO Xin;PIAO Xian-mei(State Key Laboratory of Frigid Zone Cardiovascular Diseases,Dept of Pharmacology,State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Medicine Research,Ministry of Education,College of Pharmacy,Harbin Medical University,Harbin 150086,China)

机构地区：[1]寒地心血管疾病国家重点实验室,哈尔滨医科大学药学院药理学教研室,黑龙江省生物医药工程重点实验室—省部共建国家重点实验室培育基地,心血管药物研究教育部重点实验室,黑龙江哈尔滨150086

出　　处：《中国药理学通报》2025年第1期122-130,共9页Chinese Pharmacological Bulletin

基　　金：黑龙江省中医药科研项目(No ZHY2024-221);黑龙江省自然科学基金资助项目(No LH2023H012)。

摘　　要：目的探究五味子甲素(schizandrin A,SchA)对氧化应激引起内皮功能障碍的拮抗作用及其作用机制。方法选用人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)作为研究对象,采用MTT实验检测SchA对HUVECs活力的影响;通过流式细胞技术检测细胞中ROS的含量;试剂盒检测HUVECs中MDA、CAT的含量以及细胞上清液中NO、ET-1的含量;Western blot实验检测细胞中SOD1、p-eNOS/eNOS蛋白以及Nrf2/Keap1/HO-1通路蛋白的表达情况;免疫荧光实验检测细胞Nrf2的入核情况。结果SchA通过激活Nrf2/Keap1/HO-1信号通路逆转LPS或缺氧诱导的HUVECs内ROS和MDA含量的升高及SOD1和CAT含量的下降;SchA逆转LPS诱导的HUVECs中p-eNOS和eNOS蛋白表达的降低及逆转细胞培养液中NO含量的下降和ET-1含量的升高;Nrf2抑制剂ML385逆转SchA对氧化应激及内皮功能障碍的拮抗作用。结论SchA拮抗LPS及缺氧诱导的氧化应激,SchA通过上调Nrf2/Keap1/HO-1信号通路改善氧化应激引起的内皮功能障碍。Aim To investigate the antagonistic effect of Schizandrin A(SchA)on oxidative stress-induced endothelial dysfunction and its mechanism of action.Methods Human umbilical vein endothelial cells(HUVECs)were selected as the research subjects,and the effects of SchA on cell viability were detected by MTT assay;the content of ROS in the cells was detected by flow cytometry;the content of MDA and CAT in the cells,and the content of NO and ET-1 in the cell supernatant were detected by kit assay;and the expression of SOD1,p-eNOS/eNOS proteins,and ET-1 in the cell supernatant were detected by Western blot.Immunofluorescence experiments were performed to detect Nrf2 entry into the nucleus of cells.Results SchA reversed the LPS-or hypoxia-induced increase in ROS and MDA content as well as the decrease in SOD1 and CAT content in HUVECs by activating the Nrf2/Keap1/HO-1 signaling pathway.SchA inhibited the decrease of p-eNOS and eNOS protein expression in HUVECs cells,as well as NO content in cell culture medium and the increase of ET-1 content induced by LPS.The Nrf2 inhibitor ML385 reversed the antagonistic effects of SchA on oxidative stress and endothelial dysfunction.Conclusions SchA antagonized LPS and hypoxia-induced oxidative stress,and SchA ameliorated oxidative stress-induced endothelial dysfunction by up-regulating the Nrf2/Keap1/HO-1 signaling pathway.

关 键 词：SchA 氧化应激 内皮功能障碍 Nrf2/Keap1/HO-1信号通路 HUVECS LPS 

分 类 号：R285[医药卫生—中药学]