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。

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.