Mdivi-1通过抑制少突胶质细胞凋亡信号通路发挥髓鞘保护作用  

Mdivi-1 protects oligodendrocytes through inhibiting apoptotic signaling pathway

作　　者：李艳花[1] 张晓娟 张思羽 侯惜缘 刘子乙 于晓静[2] 张年萍[1] LI Yanhua;ZHANG Xiaojuan;ZHANG Siyu;HOU Xiyuan;LIU Ziyi;YU Xiao jing;ZHANG Nianping(Medical School of Shanxi Datong University,Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases,Datong 037009,China;Medical School of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]山西大同大学医学院,老年慢性病智慧医康养大同市重点实验室,山西大同037009 [2]西安交通大学医学院,陕西西安710004

出　　处：《中国病理生理杂志》2024年第3期527-534,共8页Chinese Journal of Pathophysiology

基　　金：山西省基础研究计划项目(No.20210302123475;No.20210302123476);山西省“四个一批”科技兴医创新计划(No.2023XM033)。

摘　　要：目的:研究线粒体分裂抑制剂1(Mdivi-1)在实验性自身免疫性脑脊髓炎(EAE)小鼠髓鞘保护中的作用,探讨Mdivi-1抑制髓鞘变性的机制。方法:小鼠经髓磷脂少突胶质细胞糖蛋白第35~55位肽段(MOG35-55)免疫后,随机分为DMSO模型组和Mdivi-1干预组。于免疫后第28天处死小鼠,行Luxol fast blue染色分析髓鞘丢失情况,免疫荧光染色和TUNEL染色小鼠脊髓组织和体外细胞实验分析Mdivi-1髓鞘保护机制。结果:与DMSO模型组比较,Mdivi-1处理明显减少EAE小鼠脊髓组织白质区髓鞘丢失,减少少突胶质细胞凋亡及线粒体凋亡相关蛋白cleaved caspase-3、caspase-9、cytochrome C和Bax的表达;体外MO3.13少突胶质细胞培养实验发现,Mdivi-1可以明显阻止星形孢菌素(staurosporine)处理诱导的线粒体膜电位去极化,减轻细胞损伤,增强细胞活力。结论:Mdivi-1可能通过抑制少突胶质细胞线粒体相关凋亡信号通路发挥髓鞘保护作用。AIM:To investigate the therapeutic effect of mitochondrial fission inhibitor-1(Mdivi-1)on experi mental autoimmune encephalomyelitis(EAE)in mice,and to explore its mechanism.METHODS:The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55(MOG35-55)were randomly divided into DMSO model group and Mdivi-1 intervention group.All mice were sacrificed on the 28th day after the first immunization.The demyelination was analyzed by Luxol fast blue staining.The protective mechanism of Mdivi-1 in the spinal cord tissue was investigated by immunofluorescence staining,TUNEL staining and the in vitro experiment with MO3.13 oligodendrocytes treated with staurosporine.The mitochondrial depolarization was detected by JC-1 staining,the cell injury was checked by LDH leakage,and the viability of MO3.13 oligodendrocytes was determined by MTT assay.RESULTS:Compared with DMSO model group,the demyelinating injury was alleviated and the proportion of apoptotic CC1+oligodendrocytes in Mdivi-1 group was decreased.The cleaved caspase-3,caspase-9,cytochrome C and Bax protein expression levels in the spinal cord of Mdivi-1-treated mice was also attenuated.The in vitro MO3.13 cell experiments suggested that Mdivi-1 inhibited MO3.13 cell mitochondrial depolarization,attenuated the cell damage and increased the cell viability.CONCLUSION:Mdivi-1 pro tects against the myelin injury in EAE mice,which may be related to the suppression of oligodendrocyte apoptosis.

关 键 词：线粒体分裂抑制剂1 多发性硬化 实验性自身免疫性脑脊髓炎 细胞凋亡 少突胶质细胞 

分 类 号：R744.51[医药卫生—神经病学与精神病学] R363.2[医药卫生—临床医学] Q255[生物学—细胞生物学]