Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

作     者：WENLI JIANG JUNYI SHEN XIAOQIANG DU YAN QIU JIAN ZHONG ZHI OUYANG BINGMEI M.FU YE ZENG 

作者机构：Institute of Biomedical EngineeringWest China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu610041China Department of Biomedical EngineeringThe City College of the City University of New YorkNew York10031USA 

出 版 物：《BIOCELL》 (生物细胞（英文）)

年 卷 期：2023年第47卷第10期

页      面：2255-2263页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：funding from the National Natural Science Foundation of China(12272246) the Key Research and Development Projects of Sichuan Province(2023YFS0075) 

主　　题：Hypoxia/reoxygenation Endothelial cell Anisodine hydrobromide Muscarinic acetylcholine receptors Hypoxia-inducible factor-1α 

摘      要：Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion *** dysfunction can be caused by hypoxia/reoxygenation(H/R)via oxidative stress and metabolic *** present study investigated whether AT3 regulates the production of nitric oxide(NO)and reactive oxygen species(ROS),and the HIF-1αpathway via regulation of muscarinic acetylcholine receptors(mAChRs)in brain microvascular endothelial cells after H/R ***:Under H/R conditions,hCMEC/D3 cerebral microvascular endothelial cells were treated with *** inhibitors of M2-and M4-mAChRs were used to explore the mechanism by which AT3 influences oxidative stress in endothelial ***,mAChRs expression was detected by western blotting and NO production was detected by Greiss *** intracellular ROS level was measured using DCFH-DA *** expression of hypoxia-inducible transcription factor 1α(HIF-1α)was also ***:While H/R induced the expression of M2-and M4-mAChRs,AT3 suppressed the H/R-upregulated M2-and M4-mAChRs.H/R also induced the production of NO,ROS,and ***3 and M4-mAChR inhibitors inhibited the H/R-induced production of NO and ROS and ***-1αwas induced by H/R,but was suppressed by ***:Thus,the in vitro evidence shows that AT3 protects against H/R injury in cerebral microvascular endothelial cells via inhibition of HIF-1α,NO and ROS,predominantly through the downregulation of *** findings offer novel understandings regarding AT3-mediated attenuation of endothelial cell apoptosis and cerebral ischemia/reperfusion injury.