Wang Xue, Shi Huimin, Wei Zibin, Liu Ping, Tian Shujuan, Song Xueqin
Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Neuromolecular Med. 2025 May 20;27(1):40. doi: 10.1007/s12017-025-08865-x.
Microglia-mediated neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Studies have shown that butylphthalide (3-n-butylphthalide or NBP) can play an anti-inflammatory role in other diseases by regulating the activation of microglia. This study investigates the neuroprotective and anti-inflammatory effects of NBP in a mouse model of Parkinson's disease (PD) induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The primary aim was to determine whether NBP can improve symptoms of PD by modulating microglial activation and to explore the underlying mechanisms involved. Motor function (assessed via Open Field and Pole Climbing tests), dopaminergic neuronal loss, and activation of different microglial subtypes were assessed in control, MPTP-treated, and NBP + MPTP-treated mice. A p38 phosphorylation inhibitor + MPTP group was also established to investigate potential mechanisms of NBP action. Mice treated with NBP exhibited significantly improved motor function and reduced dopaminergic neuronal loss compared to MPTP-treated mice. In PD mice, pro-inflammatory factor expression was elevated, anti-inflammatory factor expression was reduced, and the expression of arginase-1 (arg-1), a marker for M2 microglia, was decreased. NBP treatment resulted in reduced levels of pro-inflammatory factors, increased levels of anti-inflammatory factors, and elevated arg-1 expression. Additionally, inhibition of p38 phosphorylation further decreased pro-inflammatory factor expression while increasing both anti-inflammatory factor levels and arg-1 expression. The findings indicate that NBP regulates neuroinflammation and improves symptoms of PD by promoting the transformation of microglia to the M2 phenotype, likely mediated through the p38 phosphorylation pathway.
小胶质细胞介导的神经炎症在帕金森病（PD）的发病机制中起重要作用。研究表明，丁苯酞（3 -正丁基苯酞或NBP）可通过调节小胶质细胞的激活在其他疾病中发挥抗炎作用。本研究调查了NBP在神经毒素1 -甲基- 4 -苯基- 1,2,3,6 -四氢吡啶（MPTP）诱导的帕金森病（PD）小鼠模型中的神经保护和抗炎作用。主要目的是确定NBP是否能通过调节小胶质细胞激活来改善PD症状，并探索其中涉及的潜在机制。在对照组、MPTP处理组和NBP + MPTP处理组小鼠中评估了运动功能（通过旷场试验和爬杆试验评估）、多巴胺能神经元损失以及不同小胶质细胞亚型的激活情况。还建立了p38磷酸化抑制剂 + MPTP组以研究NBP作用的潜在机制。与MPTP处理组小鼠相比，NBP处理的小鼠运动功能显著改善，多巴胺能神经元损失减少。在PD小鼠中，促炎因子表达升高，抗炎因子表达降低，且M2小胶质细胞标志物精氨酸酶-1（arg-1）的表达下降。NBP处理导致促炎因子水平降低，抗炎因子水平升高，且arg-1表达增加。此外，抑制p38磷酸化进一步降低了促炎因子表达，同时增加了抗炎因子水平和arg-1表达。这些发现表明，NBP通过促进小胶质细胞向M2表型转化来调节神经炎症并改善PD症状，这可能是通过p38磷酸化途径介导的。
