星形胶质细胞调节缺血性脑卒中的胶质瘢痕形成  

Astrocytes regulate glial scar formation in cerebral ischemic stroke

作　　者：杨婷[1] 丁智斌[1,2,3] 江楠 韩红霞 侯苗苗 马存根 宋丽娟 李新毅[1,3] Yang Ting;Ding Zhibin;Jiang Nan;Han Hongxia;Hou Miaomiao;Ma Cungen;Song Lijuan;Li Xinyi(Department of Neurology,Third Hospital of Shanxi Medical University(Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital),Taiyuan 030032,Shanxi Province,China;The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Department of Encephalopathy,First Clinical College,Shanxi University of Chinese Medicine,Jinzhong 030619,Shanxi Province,China;Key Laboratory of Cellular Physiology,Shanxi Medical University,Ministry of Education,Taiyuan 030001,Shanxi Province,China;Shanxi Cardiovascular Hospital(Affiliated Cardiovascular Hospital of Shanxi Medical University),Taiyuan 030024,Shanxi Province,China)

机构地区：[1]山西医科大学第三医院(山西白求恩医院,山西医学科学院,同济山西医院)神经内科,山西省太原市030032 [2]山西中医药大学国家中医药管理局多发性硬化益气活血重点研究室/第一临床学院脑病科,山西省晋中市030619 [3]山西医科大学细胞生理学教育部重点实验室,山西省太原市030001 [4]山西省心血管病医院(山西医科大学附属心血管病医院),山西省太原市030024

出　　处：《中国组织工程研究》2024年第1期131-138,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年科学基金项目(82004028),项目负责人:宋丽娟;中国博士后科学基金面上资助项目(2020M680912),项目负责人:宋丽娟;山西省基础研究计划自由探索类项目(20210302123408),项目负责人:丁智斌;山西省卫健委医学科技领军团队(2020TD05),项目负责人:马存根;山西医科大学第三医院人才引进科研启动金项目(2021RC033),项目负责人:丁智斌;山西中医药大学青年科学家培育项目(2021-PY-QN-09),项目负责人:宋丽娟。

摘　　要：背景:缺血性脑卒中是临床上主要的致死及致残性疾病之一,经血管再通获益的患者数量极其有限,故探索有效治疗手段迫在眉睫。以星形胶质细胞为主所形成的胶质瘢痕作为缺血性脑卒中的重要病理变化之一,是阻碍脑卒中后期轴突再生和神经修复的主要原因。目的:通过对缺血性脑卒中后星形胶质细胞瘢痕形成的病理过程、关键的信号调节机制和潜在治疗靶点进行分析,旨在为干预星形胶质细胞瘢痕形成以有效治疗缺血性脑卒中提供理论依据,并为促进脑卒中后康复提供新策略。方法:全面检索2010-2022年在中国知网、PubMed和Web of Science数据库收录的相关文献,中文检索词:“缺血性脑卒中、脑缺血、星形胶质细胞、胶质瘢痕、胶质增生、星形胶质细胞增多症”,英文检索词:“Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis”,经筛选后纳入78篇文献进行综述。结果与结论:①星形胶质细胞在中枢神经系统稳态的维持中具有重要作用,缺血性脑卒中发生后,星形胶质细胞从静息态转变为激活态,由于脑缺血部位损伤的严重程度的不同,其活化呈现从肿胀、增殖到胶质瘢痕形成的动态变化。②成熟的星形胶质细胞受到刺激重新进入细胞周期并发生增殖和迁移,是形成胶质瘢痕的主要细胞来源,脑室下区的神经干细胞、脑实质局部神经胶质抗原2(NG2)和室管膜细胞前体细胞也可分化为星形胶质细胞,内皮素1(ET-1)、水通道蛋白4(AQP4)、睫状神经营养因子(CNTF)和缝隙连接蛋白参与了此过程;硫酸软骨素蛋白多糖(CSPG)是细胞外基质的主要成分,同增殖的星形胶质细胞共同形成致密的胶质瘢痕屏障,阻碍了轴突的极化和延伸。③星形胶质细胞活化、增殖、迁移及促炎作用所涉及的关键信号分子的激活或者抑制调节了胶质瘢痕形成,转化生长因子βBACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke.OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation.METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were“Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis”in Chinese and English.Finally,78 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier

关 键 词：缺血性脑卒中 星形胶质细胞 胶质瘢痕 增殖 炎症 再生 信号通路 治疗 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364