实用医学杂志 ›› 2024, Vol. 40 ›› Issue (11): 1494-1499.doi: 10.3969/j.issn.1006-5725.2024.11.005

• 专题报道:帕金森病 • 上一篇    下一篇

电针对MPTP诱导帕金森病小鼠FoXO1/NLRP3通路介导神经炎症的影响

胡梦妮,张小蕾,荣臻,汪瑶,李亚楠,马骏()   

  1. 湖北中医药大学针灸骨伤学院 (武汉 430061 )
  • 收稿日期:2023-12-07 出版日期:2024-06-10 发布日期:2024-06-13
  • 通讯作者: 马骏 E-mail:mj-1964@163.com
  • 基金资助:
    国家自然科学基金项目(81473788);国家重点研发计划项目(2020YFC0845800)

Effects of electroacupuncture on MPTP⁃induced FoXO1/NLRP3 pathway mediated neuroinflammation in mice with Parkinson′s disease

Mengni HU,Xiaolei ZHANG,Zhen RONG,Yao WANG,Ya′nan LI,Jun. MA()   

  1. School of Acupuncture,Moxibustion and Orthopedics,Hubei University of Traditional Chinese Medicine,Wuhan 430061,China
  • Received:2023-12-07 Online:2024-06-10 Published:2024-06-13
  • Contact: Jun. MA E-mail:mj-1964@163.com

摘要:

目的 探究电针对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导帕金森病(PD)模型小鼠的作用机制是否与叉头盒蛋白O1(FoXO1)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路介导的神经炎症相关。 方法 将30只小鼠随机分为对照组(Ctrl)、模型组(MPTP)、电针组(EA),每组10只。连续7 d腹腔注射MPTP 30 mg/(kg·d)制备PD小鼠模型。采用旷场实验及爬杆实验观察小鼠行为学;免疫组化观察小鼠中脑黑质α-突触核蛋白(α-syn)表达水平;蛋白免疫印迹测定Iba-1、FoXO1、NLRP3、ASC、Caspase-1蛋白表达水平;ELISA法检测中脑黑质肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)炎症因子表达水平。 结果 MPTP组小鼠出现显著的行为学障碍,中脑黑质α-syn明显增加(P < 0.01),Iba-1、FoXO1、NLRP3、ASC、Caspase-1蛋白水平升高(P < 0.05,P < 0.01),TNF-α、IL-1β含量明显增加(P < 0.01)。EA治疗后能有效改善PD小鼠运动障碍,提高运动平衡及协调能力(P < 0.01),减少α-syn的异常聚集(P < 0.01),减轻小胶质细胞异常活化,缓解神经炎症(P < 0.05)。 结论 电针可能通过调控FoXO1/NLRP3通路介导的神经炎症,在PD中发挥保护作用。

关键词: 帕金森病, 电针, 神经炎症, 叉头盒蛋白O1, NOD样受体热蛋白结构域相关蛋白3

Abstract:

Objective To investigate whether the mechanism of action of electro-acupuncture in MPTP-induced Parkinson's disease (PD) model mice is related to neuroinflammation mediated by the forkhead box protein O1 (FoXO1)/NOD-like receptor heat protein structural domain-related protein 3 (NLRP3) signaling pathway. Methods Thirty mice were randomly divided into control (Ctrl), model (MPTP), and electro-acupuncture (EA) groups, with 10 mice in each group. PD mouse model was prepared by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 30 mg/(kg·d) for 7 d consecutively. Behavioral changes of mice were observed by open field and pole-climbing experiments; α-synuclein (α-syn) expression in the substantia nigra of the midbrain was observed by immunohistochemistry; FoXO1, NLRP3, ASC, and Caspase-1 were determined by Western blot; and the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) was detected by ELISA in the substantia nigra of the midbrain. Results Mice in the MPTP group showed significant behavioral deficits, with a significant increase in midbrain substantia nigra α-syn (P < 0.01), elevated levels of Iba-1, FoXO1, NLRP3, ASC, and Caspase-1 proteins (P < 0.05 and P < 0.01, respectively), and a significant increase in the levels of TNF-α, and IL-1β (P < 0.01).The treatment of EA was effective in improve the dyskinesia of PD mice, improve motor balance and coordination (P < 0.01), reduce the abnormal aggregation of α-syn (P < 0.01), reduce the abnormal activation of microglia, and alleviate neuroinflammation (P < 0.05). Conclusion Electro-acupuncture may play a protective role in PD by modulating FoXO1/NLRP3 pathway-mediated neuroinflammation.

Key words: Parkinson's disease, neuroinflammation, electro-acupuncture, forkhead box protein O1, NLRP3

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