小胶质细胞通过STAT3调控脊髓损伤后少突胶质祖细胞增殖  

Microglia regulates the proliferation of OPCs after spinal cord injury through STAT3

作　　者：劳泽辉 周治来 谢欢[3] 张辉 Lao Zehui;Zhou Zhilai;Xie Huan;Zhang Hui(Department of Spine and Orthopedics,Guangdong Second People's Hospital,the Second Clinical College of Southern Medical University,Guangzhou 510220,China)

机构地区：[1]南方医科大学第二临床医学院,广州510220 [2]广东省第二人民医院脊柱骨科 [3]广州暨南大学第一临床学院

出　　处：《脑与神经疾病杂志》2025年第2期115-121,共7页Journal of Brain and Nervous Diseases

基　　金：广东省自然科学基金(2016A030313627);广州市科技计划项目(202002030004);广州市科技计划项目(202201010803)。

摘　　要：目的探究脊髓损伤(SCI)后小胶质细胞(Mg)对少突胶质祖细胞(OPCs)调控作用及其可能的分子机制,为SCI的临床治疗提供实验依据。方法体外建立Mg与OPCs共培养体系,用内毒素脂多糖(LPS)活化Mg,采用免疫荧光法、蛋白质印迹法检测Mg对OPCs增殖的影响及与增殖密切相关的STAT3分子的表达情况;构建小鼠SCI模型,在损伤后不同时间点(第1、3、7、14天)检测STAT3表达变化;采用集落刺激因子1受体(CSF1R)抑制剂PLX3397清除小鼠Mg,检测其对OPCs增殖及与STAT3分子表达的关系。结果LPS刺激后,Mg胞体显著增大(P<0.05),细胞群数量显著增加(P<0.05);活化的Mg可通过激活STAT3促进OPCs的增殖(P<0.05),该功能可被STAT3抑制剂STA21阻断(P<0.05);SCI后,脊髓中STAT3分子的表达显著升高(P<0.05),并在损伤后第3天达到峰值;清除Mg可降低脊髓中STAT3的表达及少突胶质细胞(OLs)的增殖。结论Mg可能通过激活STAT3促进SCI后OPCs增殖。Objective This study aims to investigate the regulatory role of microglia(Mg)on oligodendrocyte progenitor cells(OPCs)following spinal cord injury(SCI)and explore potential molecular mechanisms.The goal is to provide a theoretical and experimental basis for the clinical treatment of SCI.Methods An in vitro co-culture system of Mg and OPCs was established.Mg were activated using lipopolysaccharide(LPS).The impact of Mg on OPC proliferation and the expression of signal transducer and activator of transcription 3(STAT3),closely associated with proliferation,were examined using immunofluorescence and Western blot methods.A mouse SCI model was created,and changes in STAT3 expression were monitored at different time points post-injury(1,3,7,14 days).The CSF1R inhibitor PLX3397 was employed to eliminate mouse microglia,and its effect on OPC proliferation and STAT3 expression was investigated.Results Following LPS stimulation,Mg cell bodies significantly enlarged(P<0.05),and the cell population increased significantly(P<0.05).Activated Mg promoted OPC proliferation through STAT3 activation(P<0.05),a function inhibited by the STAT3 inhibitor STA21(P<0.05).After SCI,STAT3 expression in the spinal cord significantly increased(P<0.05),peaking on the 3rd day post-injury.The elimination of Mg reduced STAT3 expression in the spinal cord and inhibited oligodendrocyte proliferation.Conclusion Mg may promote OPC proliferation after SCI through the activation of STAT3.

关 键 词：脊髓损伤 小胶质细胞 少突胶质祖细胞 STAT3 

分 类 号：R744[医药卫生—神经病学与精神病学]