脑肾素-血管紧张素系统通过脑微血管内皮细胞调控神经血管单元介导阿尔茨海默病机制研究进展  

Brain renin-angiotensin system mediates Alzheimer disease by regulating neurovascular units via brain microvascular endothelial cells:a review

作　　者：张评奥 宋成寰 施霁耘 黄婉莹 张瑞 张永芳[1,2] 王昊 ZHANG Pingao;SONG Chenghuan;SHI Jiyun;HUANG Wanying;ZHANG Rui;ZHANG Yongfang;WANG Hao(Department of Pharmacology and Chemical Biology,School of Medicine,Shanghai Jiaotong University,Shanghai 200025,China;Shanghai Universities Collaborative Innovation Center for Translational Medicine,School of Medicine,Shanghai Jiaotong University,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院药理学与化学生物学系,上海200025 [2]上海交通大学医学院、上海高校转化医学协同创新中心,上海200025

出　　处：《中国药理学与毒理学杂志》2023年第10期781-791,共11页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81973297);国家自然科学基金(82073836);国家自然科学基金(81872841);国家自然科学基金(82003719);上海市科委重点项目(19JC1413100);上海交通大学“医学转化交叉基金”(ZH2018ZDA23)。

摘　　要：脑血管功能异常是阿尔茨海默病(AD)重要的病理特征之一,而脑肾素-血管紧张素系统(BRAS)病理改变则是AD患者脑血管损伤的重要指标。BRAS相对独立于外周肾素-血管紧张素系统(RAS),并可通过调节神经元和胶质细胞影响神经血管单元(NVU)稳态。脑微血管内皮细胞是NVU的重要成员,由其构成的血脑屏障可能是实现外周RAS与BRAS调控的重要桥梁。本文围绕AD分别介绍BRAS对神经元功能、血管内皮细胞发育及星形胶质细胞和小胶质细胞稳态的影响,从细胞的能量代谢、氧化应激和炎症反应等角度综述BRAS在NVU调节互作网络及在AD病理中的作用。综述RAS药物的临床研究和RAS在AD中的研究进展,以期阐明BRAS对NVU的调控机制及其对AD病理的贡献,为AD的预防和治疗提供新思路。Cerebrovascular dysfunction is one of the main features of Alzheimer disease(AD).And the pathological change of the renin-angiotensin system(RAS)is an important indicator of vascular injury in AD patients.Brain RAS(BRAS)is independent of peripheral RAS and is capable of regulating neurons and glial cells,which is of great significance for the regulation of the neurovascular unit(NVU).The brain microvascular endothelial cells(BMECs)are important members of NVU.The blood-brain barriers composed of BMECs make it a pivotal link connecting the peripheral RAS with BRAS.This paper reviews the impact of BRAS on functions of neurons,BMECs and glial cells in AD as well as its contributions to the NVU.BRAS harmonizes AD pathology through energy metabolism,oxidative stress,and inflamma⁃tory response.Furthermore,this review summarizes the RAS antagonist agents used in clinic trials to emphasize the important role of BRAS in NVU regulation in AD.

关 键 词：肾素-血管紧张素系统 神经血管单元 阿尔茨海默病 脑微血管内皮细胞 

分 类 号：R964[医药卫生—药理学] R963[医药卫生—药学]