富马酸二甲酯通过激活自噬调控小胶质细胞炎症表型转化  

Dimethyl Fumarate Regulates the Inflammatory Phenotype Transformation of Microglia via Activating Autophagy

作　　者：诸丽芳 张航 庞晓伟[1,2] 初云惠 张璐阳 秦川 田代实 ZHU Lifang;ZHANG Hang;PANG Xiaowei;CHU Yunhui;ZHANG Luyang;QIN Chuan;TIAN Daishi(Department of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Hubei Key Laboratory of Neural Injury and Functional Reconstruction,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]华中科技大学神经损伤与功能重建湖北省重点实验室,武汉430030

出　　处：《神经损伤与功能重建》2025年第2期63-66,78,共5页Neural Injury and Functional Reconstruction

基　　金：国家自然科学基金项目(自噬介导小胶质细胞代谢重编程参与慢性低灌注脑白质损伤的机制研究,No.82071380)。

摘　　要：目的:体外探究慢性低灌注白质损伤下富马酸二甲酯(dimethyl fumarate,DMF)对小胶质细胞表型转化的作用及机制。方法:通过糖氧剥夺及外源性髓鞘碎片刺激,构建慢性低灌注白质脱髓鞘模型,给予DMF干预小胶质细胞。采用实时荧光定量PCR、转录组测序及免疫荧光染色的方法探究小胶质细胞炎症表型转化。结果:①与对照组相比,给予DMF后,促炎基因白细胞介素(IL)-6、IL-1β和肿瘤坏死因子(TNF)-α的表达均显著降低(P<0.05);②转录组分析显示DMF处理后小胶质细胞的神经炎症相关通路下调,同时自噬相关通路上调;③与对照组相比,DMF干预组自噬相关基因和蛋白表达明显上调(P<0.05)。结论:DMF可能通过激活自噬通路调控小胶质细胞由促炎表型向抗炎表型转化。Objective:To explore in vitro the effect and mechanism of dimethyl fumarate(DMF)on modulat-ing microglial polarization under chronic hypoperfusion-induced white matter injury(WMI).Methods:An in vitro model of low perfusion white matter demyelination was established by glucose-oxygen deprivation and stimulation with exogenous myelin debris,combined with DMF intervention in microglial cells.Real-time quan-titative PCR,transcriptome sequencing,and immunofluorescence staining were employed to investigate the in-flammatory phenotype transformation of microglia.Results:(1)Compared to the control group,the expression of pro-inflammatory genes interleukin(IL)-6,IL-1βand tumor necrosis factor(TNF)-αsignificantly decreased after DMF administration(P<0.05);(2)Transcriptome analysis revealed downregulation of neuroinflamma-tionrelated pathways and upregulation of autophagy-related pathways in microglia after DMF treatment;(3)Compared to the control group,the expression of autophagy-related genes and proteins was significantly in-creased in the DMF intervention group(P<0.05).Conclusion:DMF may regulate the transformation of microg-lia from a pro-inflammatory to an anti-inflammatory phenotype by activating the autophagy pathway.

关 键 词：小胶质细胞 富马酸二甲酯 自噬 炎症表型 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学] R743R744