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 |
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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) |
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摘要点击次数: 363 |
全文下载次数: 309 |
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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