The abnormal production of short chain fatty acid (SCFAs) caused by gut microbial dysbiosis plays an important role in the pathogenesis and progression of Parkinson’s disease (PD). This study sought to evaluate how butyrate, one of SCFAs, affect the pathology in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treated mouse model of PD. Sodium butyrate (NaB; 165 mg/kg/day i.g., 7 days) was administrated from the day after the last MPTP injection. Interestingly, NaB significantly aggravated MPTP-induced motor dysfunction (P < 0.01), decreased dopamine (P < 0.05) and 5-HT (P < 0.05) levels, exacerbated declines of dopaminergic neurons (34%, P < 0.05) and downregulated expression of tyrosine hydroxylase (TH, 47%, P < 0.05), potentiated glia-mediated neuroinflammation by increasing the number of microglia (17%, P < 0.05) and activating astrocytes (28%, P < 0.01). In vitro study also confirmed that NaB could significantly exacerbate pro-inflammatory cytokines expression (IL-1β, 4.11-fold, P < 0.01; IL-18, 3.42-fold, P < 0.01 and iNOS, 2.52-fold, P < 0.05) and NO production (1.55-fold, P < 0.001) in LPS-stimulated BV2 cells. In addition, NaB upregulated the expression of pro-inflammatory cytokines (IL-6, 3.52-fold, P < 0.05; IL-18, 1.72-fold, P < 0.001) and NLRP3 (3.11-fold, P < 0.001) in the colon of PD mice. However, NaB had no effect on NFκB, MyD88 and TNF-α expression in PD mice. Our results indicate that NaB exacerbates MPTP-induced PD by aggravating neuroinflammation and colonic inflammation independently of the NFκB/MyD88/TNF-α signaling pathway.

肠道微生物菌群失调引起的短链脂肪酸（SCFAs）异常产生在帕金森病（PD）的发病机制和进展中起重要作用。本研究旨在评估丁酸盐（一种 SCFA）如何影响亚急性 1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐 (MPTP) 治疗的 PD 小鼠模型中的病理学。从最后一次MPTP注射后的第二天开始施用丁酸钠(NaB；165mg/kg/天，ig . ，7天)。有趣的是，NaB 显着加重 MPTP 引起的运动功能障碍（P  < 0.01），降低多巴胺（P  < 0.05）和 5-HT（P  < 0.05）水平，加剧多巴胺能神经元的衰退（34%，P < 0.05) 和酪氨酸羟化酶的表达下调 (TH, 47%, P  < 0.05)，通过增加小胶质细胞的数量 (17%, P  < 0.05) 和激活星形胶质细胞 (28%, P  < 0.01)来增强胶质细胞介导的神经炎症. 体外研究还证实，NaB 可显着加剧促炎细胞因子的表达（IL-1β，4.11 倍，P  < 0.01；IL-18，3.42 倍，P  < 0.01 和 iNOS，2.52 倍，P  < 0.05） LPS 刺激的 BV2 细胞中NO 产生（1.55 倍，P  < 0.001）。此外，NaB 上调促炎细胞因子的表达（IL-6，3.52 倍，P  < 0.05；IL-18，1.72 倍，P < 0.001）和 NLRP3（3.11 倍，P  < 0.001）在 PD 小鼠的结肠中。然而，NaB 对 PD 小鼠的 NFκB、MyD88 和 TNF-α 表达没有影响。我们的结果表明，NaB 通过独立于 NFκB/MyD88/TNF-α 信号通路加重神经炎症和结肠炎症来加剧 MPTP 诱导的 PD。