中国药物警戒 ›› 2020, Vol. 17 ›› Issue (11): 753-757.
DOI: 10.19803/j.1672-8629.2020.11.02

• 基础与临床研究 • 上一篇    下一篇

天麻联苄化合物20C对MPTP/p诱导帕金森病小鼠模型的作用及机制

周甜甜, 张秋双, 陈颖, 朱承根, 石建功, 陈乃宏, 苑玉和*   

  1. 中国医学科学院药物研究所,北京 100050
  • 收稿日期:2020-11-10 修回日期:2020-11-10 出版日期:2020-11-15 发布日期:2020-11-10
  • 通讯作者: *苑玉和,女,博士,研究员·博导,神经药理学和抗帕金森病创新药物研制及作用机制研究。E-mail：yuanyuhe@imm.ac.cn
  • 作者简介:周甜甜,女,在读硕士,神经药理学。
  • 基金资助:
    国家自然基金面上项目（81773925）; 重大新药创制（2018ZX09711001-003-005）

Effects of Bibenzyl Compound (20C) from Gastrodia elata on MPTP/p-induced Mice and Mechanism

ZHOU Tiantian, ZHANG Qiushuang, CHEN Ying, ZHU Chenggen, SHI Jiangong, CHEN Naihong, YUAN Yuhe*   

  1. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050
  • Received:2020-11-10 Revised:2020-11-10 Online:2020-11-15 Published:2020-11-10

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摘要： 目的 从病理、生化两方面研究天麻联苄化合物20C对帕金森病（parkinson's disease, PD）小鼠模型的作用及机制。方法 通过皮下注射丙磺舒、腹腔注射MPTP制备1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP）联合丙磺舒（probenecid）模型,诱导PD小鼠模型;通过HE染色和免疫组化的方法评价组织病理改变;通过Western blot方法检测蛋白水平变化。结果 病理生化结果显示,20C可以减少MPTP诱导的胃部硝基化α-突触核蛋白（nitrated-α-synuclein）。Western blot结果显示,20C可以降低MPTP诱导的肠道Toll样受体4（Toll-like receptors 4,TLR4）水平,降低磷酸化核转录因子（nuclear factor-κB,NF-κB）p65（p-p65）水平,降低白介素1β（interleukin-1β,IL-1β）水平,减轻炎症反应。结论 20C可以减少α-突触核蛋白聚集体和硝基化形式的生成,同时可以抑制TLR4-NF-κB p65通路,抑制p65的活化,减少IL-1β的生成,抑制炎症反应,对MPTP/p诱导的PD小鼠发挥保护作用。

关键词: 帕金森病, MPTP/p, 天麻联苄化合物20C, α-突触核蛋白

Abstract: Objective To study the pathological and biochemical effect of bibenzyl compound 20C on the mouse model of MPTP/p (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP/probenecid) and explore the mechanism. Methods A mouse model of MPTP/p was established. Mice received an intraperitoneal injection of MPTP and subcutaneous injection of probenecid. Pathological changes were examined by HE staining and immunohistochemistry while biochemical changes were detected by Western blot. Results Pathological and biochemical results showed that 20C could reduce expressions of MPTP/p-induced nitrated-α-synuclein in the stomach. The results of Western blot suggested that 20C reduced the level of Toll-like receptors 4 (TLR4) in the MPTP/p model, decreased phosphorylated nuclear factor-κB (NF-κB) p65 (p-p65), inhibited interleukin-1β (IL-1β) generation, and ameliorated inflammation. Conclusion 20C can reduce the formation of α-synuclein aggregation and nitrated-α-synuclein, inhibit TLR4-NF-κB p65 pathway, prevent p65 from aetivation, decrease IL-1β, inhibit inflammation and protect mice from MPTP toxicity.

Key words: Parkinson's disease, MPTP/p, bibenzyl compound 20C from Gastrodia elata, α-synuclein

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