中国药物警戒 ›› 2021, Vol. 18 ›› Issue (4): 320-323.
DOI: 10.19803/j.1672-8629.2021.04.05

• 帕金森病药物研究模型专栏 • 上一篇    下一篇

MPTP诱导帕金森病小鼠胃肠道中单胺类递质及胶质细胞变化

温路1,2, 王硕1, 张程璐1, 陈乃宏1, 苑玉和1,*   

  1. 1中国医学科学院药物研究所,北京 100050;
    2中国医学科学院北京协和医院,北京 100050
  • 收稿日期:2021-01-08 出版日期:2021-04-15 发布日期:2021-04-23
  • 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:温路,女,硕士,药理学。
  • 基金资助:
    国家自然科学基金项目（81773925）; 北京市自然基金（7212156）

Changes of Monoamine Transmitters in the Gastrointestinal Tract and Gastrointestinal Glial Cells of MPTP Induced Parkinson's Disease Mice

WEN Lu1,2, WANG Shuo1, ZHANG Chenglu1, CHEN Naihong1, YUAN Yuhe1,*   

  1. 1Institute of Materia Medica, Beijing 100050, China;
    2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
  • Received:2021-01-08 Online:2021-04-15 Published:2021-04-23

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摘要： 目的 探究帕金森病（Parkinson's disease, PD）小鼠模型胃肠道中的单胺类神经递质和胃肠胶质细胞（enteric glial cells, EGC）的改变。方法 腹腔注射丙磺舒（probenecid）后皮下注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP）制备PD野生型小鼠和A53T转基因小鼠模型;通过高效液相色谱法（high-performance liquid chromatography, HPLC）检测小鼠胃肠道中神经递质的变化;免疫荧光评价胃肠胶质细胞的变化。结果 HPLC结果显示,MPTP降低野生型和A53T转基因小鼠胃肠道中去甲肾上腺素（norepinephrine, NE）的递质水平,提高多巴胺（dopamine, DA）的毒性代谢物二羟基苯乙醛（dihydroxy phenylacetaldehyde, DOPAL）的含量,但对DA及其代谢产物二羟基苯乙酸（dihy-droxyphenylacetic acid, DOPAC）和高香草酸（homovanillic acid, HVA）的递质水平无显著影响;免疫荧光结果显示EGC神经胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）表达升高。结论 MPTP可以促使外周胃肠道NE的递质水平降低和EGC的激活,这可能与PD早期出现的胃肠功能障碍相关。

关键词: 帕金森病, 1-甲基-4-苯基-1,2,3,6-四氢吡啶, 胃肠道, 单胺递质, 神经胶质细胞

Abstract: Objective To explore the changes of monoamine neurotransmitters and enteric glial cells (EGC) in the gastrointestinal tract of Parkinson’s disease (PD) mice. Methods The PD models of wild-type mice and A53T transgenic mice were made by gaving mice intraperitoneal injections of probenecid, followed by subcutaneous injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The changes of neurotransmitters in the gastrointestinal tract of mice were detected by high-performance liquid chromatography (HPLC) and the changes of gastrointestinal glial cells were evaluated by immunofluorescence. Results HPLC results showed that MPTP reduced the level of norepinephrine (NE) and increased the level of dihydroxy phenylacetaldehyde (DOPAL) of toxic metabolite of dopamine (DA). but it was no significant effect on the transmitter levels of DA and its metabolites which are dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The results of immunofluorescence showed the expression of glial fibrillary acidic protein (GFAP) in intestinal glial cells increasing. Conclusion MPTP can induce the decrease of NE neurotransmitter levels in the peripheral gastrointestinal tract and the activation of gastrointestinal glial cells, which may be related to gastrointestinal dysfunction in the early stage of PD.

Key words: Parkinson's disease, MPTP, gastrointestinal tract, monoamine transmitter, enteric glial cells

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