文章摘要
诸丽芳, ,张航, ,庞晓伟, ,初云惠, ,张璐阳, ,秦川, ,田代实,.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[J].神经损伤功能重建,2025,(2):63-66
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 viaActivating Autophagy
  
DOI:
中文关键词: 小胶质细胞  富马酸二甲酯  自噬  炎症表型
英文关键词: microglia cells  dimethyl fumarate  autophagy  inflammatory phenotype
基金项目: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)
作者单位
诸丽芳1,2 ,张航1,2 ,庞晓伟1,2 ,初云惠1,2 ,张璐阳1,2 ,秦川1,2 ,田代实1,2 1. 华中科技大学同 济医学院附属同济 医院神经内科 2. 华中科技大学神 经损伤与功能重建 湖北省重点实验室 
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中文摘要:
      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。
英文摘要:
      To explore in vitro the effect and mechanism of dimethyl fumarate (DMF) on modulating 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 quantitative PCR, transcriptome sequencing, and immunofluorescence staining were employed to investigate the inflammatory phenotype transformation of microglia. Results: (1) Compared to the control group, the expression of pro-inflammatory genes interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α significantly decreased after DMF administration (P<0.05); (2) Transcriptome analysis revealed downregulation of neuroinflammation-related 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 increased in the DMF intervention group (P<0.05). Conclusion: DMF may regulate the transformation of microglia from a pro-inflammatory to an anti-inflammatory phenotype by activating the autophagy pathway.
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