摘要
自噬是一种保守的溶酶体降解途径,能够降解和回收长寿蛋白或错误折叠的蛋白质和受损的细胞器,以维持细胞的能量和功能。脑血管内皮细胞是神经血管单元(NVU)的重要组成部分,其紧密连接结构是血脑屏障(BBB)的主要结构,而BBB完整性是维持中枢神经系统(CNS)稳态的保障。缺血性脑卒中(CIS)发生时,多种脑内细胞自噬可被激活,包括脑血管内皮细胞、神经元、小胶质细胞和星形胶质细胞等,其中脑血管内皮细胞自噬可影响BBB完整性、细胞凋亡和炎症反应。研究发现,脑血管内皮细胞自噬的激活或抑制可能与沉默信息调节因子1(SIRT-1)/叉头蛋白O3a(FOXO3a)、磷酸肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素机械靶蛋白(mTOR)、核因子κB(NF-κB)等信号通路有关,且调控脑血管内皮细胞自噬可降低细胞凋亡率、减轻炎症反应和保护BBB的完整性,从而减轻脑缺血缺氧和再灌注损伤。本文从CIS病理过程、脑血管内皮细胞自噬及其发生机制、脑血管内皮细胞自噬在CIS病理过程中的作用进行了综述,认为调控脑血管内皮细胞自噬可能是治疗CIS的一种潜在有效方法。
Autophagy is a conserved lysosomal degradation pathway that can degrade and recover long-lived or misfolded proteins and damaged organelles to maintain cellular energy and function.Cerebral vascular endothelial cells are an important part of the neurovascular unit(NVU),and their tightly connected structure is the main structure of the blood-brain barrier(BBB),and the integrity of BBB is the guarantee of maintaining the homeostasis of the central nervous system(CNS).When cerebral ischemic stroke(CIS)occurs,autophagy can be activated in a variety of brain cells,including cerebral vascular endothelial cells,neurons,microglia and astrocytes,among which cerebral vascular endothelial autophagy can affect BBB integrity,apoptosis and inflammation.Studies have shown that the activation or inhibition of autophagy in cerebral vascular endothelial cells may be related to silence information regulator 1(SIRT-1)/forkhead box protein O3a(FOXO3a),phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mechanistic target of rapamycin(mTOR),nuclear factor kappa-B(NF-κB)and other signaling pathways,and regulation of cerebral vascular endothelial autophagy can reduce the apoptosis rate,reduce inflammation and protect the integrity of BBB,thereby reducing cerebral ischemia,hypoxia and reperfusion injury.This article reviewed the pathological process of CIS,autophagy of cerebral vascular endothelial cells and its pathogenesis,and the role of cerebral vascular endothelial autophagy in the pathological process of CIS,and concluded that regulation of cerebral vascular endothelial autophagy may be a potential effective method for the treatment of CIS.
作者
戴瑶瑶
舒梦琦
魏汝恒
苗珠月
宋丽娟
马东
黄建军
马存根
DAI Yaoyao;SHU Mengqi;WEI Ruheng;MIAO Zhuyue;SONG Lijuan;MA Dong;HUANG Jianjun;MA Cungen(Research Center of Neurobiolog,Shanxi University of Chinese Medicine/the Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine,Jinzhong 030619,China;Ministry of Education Key Laboratory of Cell Physiology,Shanxi Medical University,Taiyuan 030001,China;Department of Neurosurgery,General Hospital of Sinopharm Tongmei Group,Datong 037003,China;Institute of Brain Science,Shanxi Datong University,Datong 037009,China)
出处
《实用心脑肺血管病杂志》
2024年第1期129-133,共5页
Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease
基金
国家自然科学基金资助项目(82004028,81473577)
中国博士后科学基金面上资助项目(2020M680912)
国家中医药管理局科技司“张仲景传承与创新专项”(GZY-KJS-2022-048-1)
山西省科技创新人才团队青年项目(202204051001028)
山西中医药大学2022年度科技创新团队项目(2022TD2010)
山西省医学科技创新团队项目(2020TD05)
山西中医药大学附属医院国家区域中医医疗中心心血管专项基金项目(XGZX202115)
山西中医药大学科技创新能力培育计划“青年科学家培育专题”项目(2021PY-QN-09)。
关键词
缺血性卒中
脑血管内皮细胞
自噬
细胞凋亡
炎症
血脑屏障
综述
Ischemic stroke
Cerebral vascular endothelial cells
Autophagy
Apoptosis
Inflammation
Blood-brain barrier
Review
