激活素A通过少突胶质细胞ACVR1C改善缺血性卒中小鼠神经功能的预后  

Activin A improves the outcomes of neurological function in mice with ischemic stroke through ACVR1C of oligodendrocytes

作　　者：李雨喋 王宏宇 韩松[1] 李俊发[1] LI Yudie;WANG Hongyu;HAN Song;LI Junfa(Department of Neurobiology,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学神经生物学系,北京100069

出　　处：《基础医学与临床》2023年第3期380-385,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(8217050908)。

摘　　要：目的 探讨缺血性卒中损伤过程中,激活素A的1C型受体(ACVR1C)在小鼠脑白质再髓鞘化和神经功能预后中的作用。方法 小鼠随机分为空病毒载体假手术组、腺相关病毒(AAV)假手术组、空病毒载体模型组、AAV模型组、空病毒载体激活素A组、AAV激活素A组。建立Acvr1c^(flox/flox)小鼠大脑中动脉闭塞/再灌注(MCAO/R) 1至10 d的缺血性卒中模型,注射带cre重组酶的AAV-PDGFRα-cre和AAV-PLP-cre于小鼠侧脑室,条件性敲除少突胶质前体细胞和少突胶质细胞上Acvr1c。神经功能评分观察神经功能的预后;Western bolt检测ACVR1C蛋白和髓鞘碱性蛋白(MBP)的表达。结果 随着再灌注时间的延长,激活素A在第7天时通过少突胶质细胞上的ACVR1C改善小鼠的行为学结果(P<0.05),在第10天时明显提高小鼠胼胝体中MBP蛋白表达水平(P<0.05)。结论 激活素A通过作用于少突胶质细胞上ACVR1C,促进缺血性卒中小鼠白质再髓鞘化并改善神经功能的预后。Objective The role of activin A receptor type 1C(ACVR1C) in white matter remyelination and neurological outcome of mice with ischemic stroke were investigated.Methods Mice were randomly divided into empty virus vector sham operation group,adeno-associated virus(AAV) sham operation group,empty virus vector model group,AAV model group,empty virus vector activin group A and AAV activin group A.Acvr1c^(flox/flox) mice with middle cerebral artery oclusion-reperfusion(MCAO/R) for 1 to 10 days were established.Adeno-associated virus AAV-PDGFRα-cre and AAV-PLP-cre with cre recombinase were injected into the lateral ventricles of the mice.Conditional knockout of Acvr1c on oligodendrocytes and oligodendrocytes.Neurological function score was used to observe the prognosis of neurological function.The expressions of ACVR1C protein and myelin basic protein(MBP) were detected by Western blot.Results With the extension of reperfusion time,activin A improved thebehavioral outcome of mice by ACVR1C on oligodendrocytes at day 7(P<0.05),and significantly increased the expression of MBP protein in corpus callosum at day 10(P<0.05).Conclusions Activin A promotes white matter remyelination and improves outcomes of neurological function of ischemic stroke mice by acting on ACVR1C on oligodendrocytes.

关 键 词：缺血性卒中 激活素A 白质再髓鞘化 激活素1C型受体(ACVR1C) 预后 

分 类 号：R743.3[医药卫生—神经病学与精神病学]