Improvement effect of acupuncture on locomotor function in Parkinson disease via regulating gut microbiota and inhibiting inflammatory factor release / 针灸推拿医学（英文版）

ABSTRACT

Objective: To observe the effect of acupuncture on the intestinal flora in Parkinson disease (PD) model mice and explore the mechanism of acupuncture in improving the locomotor function in PD. Methods: Thirty-two C57BL/6 mice were randomly divided into a control group, a 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) group, a MPTP + acupuncture group (MPTP+A), and a MPTP + madopar group (MPTP+M), with 8 mice in each group. Except for the control group, the other groups were intraperitoneally injected [25 mg/(kg·bw)] with MPTP to establish PD mouse models. After successful modeling, the MPTP group received no intervention, the MPTP+A received acupuncture at Tianshu (ST25), Guanyuan (CV4), and Zusanli (ST36), and the MPTP+M was given madopar [125 mg/(kg·bw)] by intragastric gavage. After consecutive 10-day interventions, the intestinal function and behaviors of the mice were detected. The 16S rRNA gene sequence was used to analyze the composition of fecal intestinal flora in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay were used to detect the expression levels of inflammatory cytokines in the brain and serum. The expression levels of tyrosine hydroxylase (TH) and α-synuclein in the substantia nigra (SN) were detected by immunohistochemical staining. Toll-like receptor (TLR) 2 and lipopolysaccharide receptor CD14 (CD14) in the SN were determined by RT-qPCR. Myeloid differentiation factor (MyD) 88, nuclear factor kappa-B (NF-κB) and Akt1 in the SN were detected by Western blotting. Results: After the intervention, compared with the control group, the intestinal motility, fecal water content, and the expression of TH in the SN were significantly decreased in the MPTP group (P<0.05), along with an increased α-synuclein expression (P<0.05). Additionally, the results of the fecal microflora test showed that the alpha diversity of the MPTP decreased, and the levels of inflammatory cytokines [tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, and IL-6] in the serum and SN, and the expression of NF-κB in the SN were significantly increased (P<0.05). Compared with the MPTP group, acupuncture intervention significantly enhanced the autonomous horizontal movement and coordination ability of PD mice (P<0.05); acupuncture and madopar interventions significantly reduced the levels of α-synuclein, inflammatory cytokines (TNF-α, iNOS, IL-1β, and IL-6) in the serum and SN, and the NF-κB expression in the SN, along with significantly increased alpha diversity richness index (P<0.05). In addition, the relative abundance of Bacteroides increased significantly in the MPTP+A (P<0.05), while the relative abundance of Firmicutes and Cyanobacteria decreased significantly (P<0.05). Conclusion: Acupuncture intervention can improve locomotor function, reduce α-synuclein aggregation and inflammatory factors expression, and increase the Akt signaling pathway in PD mice. In addition, acupuncture intervention can benignly regulate the intestinal flora of PD mice. Therefore, it suggests that acupuncture intervention can protect PD model mice probably by regulating intestinal flora and activating Akt signaling pathway.