脑血管再生修复的细胞基础和分子调控机制  

The cellular and molecular mechanisms of cerebrovascular regeneration and repair

作　　者：陈静影 刘赤 罗凌飞 CHEN JingYing;LIU Chi;LUO LingFei(Institute of Green and Intelligent Technology,Chinese Academy of Sciences,Chongqing 400714,China;Institute of Developmental Biology and Regenerative Medicine,Southwest University,Chongqing 400715,China;Department of Nephrology,Xinqiao Hospital,Army Medical University,Chongqing 400037,China)

机构地区：[1]中国科学院重庆绿色智能技术研究院,重庆400714 [2]西南大学发育生物学与再生医学研究中心,重庆400715 [3]中国人民解放军陆军军医大学第二附属医院肾内科,重庆400037

出　　处：《中国科学：生命科学》2022年第5期618-632,共15页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:31730060,32000576,31771609)资助。

摘　　要：缺血性脑卒中是一种急性脑血管疾病,会导致局部脑血管网和神经元大量死亡并产生脑水肿.对于缺血性脑卒中的治疗主要包括超急性期的血管再通以及后期的促血管再生.促血管再生目前主要通过联合应用血管内皮生长因子、神经血管靶向指引分子,移植内皮前体细胞等方法,以促进血管再生修复.周细胞在脑血管再生修复过程中具有促进血管生成,参与血脑屏障重建的作用.血小板在脑血管损伤后会激活释放微颗粒,促进神经血管再生.最新发现的脑膜淋巴管在脑缺血后能侵入受损脑实质缓解脑水肿,并作为“生长轨道”指引新生血管生长.这些细胞功能提示,周细胞、血小板和脑膜淋巴管可以作为潜在的促脑血管再生的新靶标.除了以脑卒中为代表的急性脑血管病外,以脑微出血为代表的慢性脑血管病的存在更广泛,脑微出血是由脑部微小血管断裂所致.近年来发现,微血管断裂后,以小胶质细胞为代表的巨噬细胞能通过物理黏附和机械力牵引介导断裂脑微血管重新连接修复.本文旨在对现阶段脑血管再生修复过程中的细胞基础和分子调控机制进行阐述,并对未来的机制研究和治疗策略进行展望.Stroke is a severe acute cerebrovascular disease that can cause a number of neuronal deaths and brain edema.The treatment of ischemic stroke mainly includes hyperacute vascular recanalization and later pro-angiogenesis therapy.At present,the promotion of angiogenesis is mainly through the combined application of vascular growth factors and guidance molecules,and the transplantation of endothelial progenitor cells to promote vascular regeneration and repair.Pericytes can promote angiogenesis and rebuild brainblood-barrier.Activated platelets shed microparticles,which contain a variety of growth factors central to angiogenesis and neurogenesis during brain vascular regeneration.The newly discovered meningeal lymphatic vessels can invade the injured parenchyma to resolve edema and act as“growing tracks”to guide the growth of nascent blood vessels.These functions of pericytes,platelets,and the meningeal lymphatics suggest their potential as novel pro-angiogenic targets for ischemic stroke.In addition to ischemic stroke,microbleeds resulting from ruptures in microvessels are also a very extensive chronic cerebrovascular disease.After cerebral microbleeds,microglia can mediate the repair of brain vascular rupture through direct physical adhesion and mechanical traction.Here,we review the cellular and molecular mechanisms in cerebral vascular regeneration and repair.In addition,we provide our perspectives for future mechanistic studies and treatment strategies for neurovascular diseases.

关 键 词：脑血管再生修复 指引分子 内皮前体细胞 周细胞 血小板 脑膜淋巴管 小胶质细胞 

分 类 号：R743.3[医药卫生—神经病学与精神病学]