神经干细胞来源外泌体对脑缺血再灌注损伤大鼠星形胶质细胞TGF⁃β1信号转导与炎症因子的影响  

Effects of exosomes derived from neural stem cells on TGF⁃β1 signal transduction of astrocytes and inflam⁃matory factors after cerebral ischemia⁃reperfusion injury in rats

作　　者：陈珊 朱俊德 赵雪 刘若静 龙婷婷 CHEN Shan;ZHU Junde;ZHAO Xue;LIU Ruojing;LONG Tingting(Department of Human Anatomy,Basic Medical College,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]贵州医科大学基础医学院人体解剖学教研室,贵阳550025

出　　处：《实用医学杂志》2023年第13期1600-1605,1613,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81660243);贵州省自然科学基金项目(编号:黔科合基础⁃ZK[2021,2023]一般415,323);贵州医科大学国家自然基金培育项目(编号:20NSP006)。

摘　　要：目的探讨神经干细胞来源外泌体(NSC⁃Exos)对脑缺血再灌注损伤大鼠星形胶质细胞TGF⁃β1信号转导及炎症因子的影响。方法40只SD大鼠随机分为Sham组、MCAO组、PBS组和NSC⁃Exos组。建立MCAO模型,侧脑室注射NSC⁃Exos,3 d后检测大鼠神经功能缺陷评分,取脑进行相对梗死体积测定、组织病理学、IL⁃6、IL⁃1β、TGF⁃β1蛋白表达检测,以及MAP⁃2和外泌体标记探针PKH26共定位检测。结果NSC⁃Exos干预降低损伤大鼠神经功能缺陷评分和脑梗死体积(P<0.05),大鼠海马CA3区神经元数量增加,GFAP阳性细胞表达率和神经元细胞凋亡指数降低(P<0.05),蛋白IL⁃6、IL⁃1β表达下降,而TGF⁃β1表达增加(P<0.05);PKH26和MAP⁃2双阳性细胞在海马CA3区表达。结论NSC⁃Exos可能通过影响星形胶质细胞TGF⁃β1信号转导,抑制星形胶质细胞增生与炎症因子IL⁃6、IL⁃1β的表达,通过增强TGF⁃β1的表达来修复脑损伤。Objective To investigate the effects of neural stem cell⁃derived exosomes(NSC⁃Exos)on TGF⁃β1 signal transduction and inflammatory factors in astrocytes during cerebral ischemia⁃reperfusion injury in rats.Methods 40 SD rats were randomly divided into Sham group,MCAO group,PBS group and NSC⁃Exos group.The rat model of MCAO was established.NSC⁃Exos was injected into right lateral ventricle.After 3 days,the neural deficit score was performed,and the brain was taken for relative infarct volume determined,histopathology and expression detection of IL⁃6,IL⁃1β,and TGF⁃β1 protein respectively.The colocalization of MAP⁃2 and exosome⁃labeled probe PKH26 was detected.Results NSC⁃Exos intervention could reduce the neurological deficit score and cerebral infarction volume(P<0.05),increase the number of neurons,reduce the expression rate of GFAP positive cells and neuronal apoptosis index(P<0.05),and decrease the expression of protein IL⁃6 and IL⁃1β.TGF⁃β1 expression was increased(P<0.05).PKH26 and MAP⁃2 positive cells were colocalized in CA3 region of hippocampus.Conclusions NSC⁃Exos may inhibit TGF⁃β1 signaling in astrocytes and repair brain injury by reducing astrogliosis and expression of inflammatory factors while enhancing the expression of TGF⁃β1.

关 键 词：外泌体 脑卒中 星形胶质细胞 TGF⁃β1 炎症因子 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]