MPTP诱导野生型和A53T转基因型小鼠帕金森病模型纹状体中神经递质变化  

Changes of Neurotransmitters in the Striatum of MPTP-induced Wild-type and A53T Transgenic Mouse Parkinson's Disease Models

作　　者：王硕 温路 张程璐 王茹璇 陈乃宏[1] 苑玉和[1] WANG Shuo;WEN Lu;ZHANG Chenglu;WANG Ruxuan;CHEN Naihong;YUAN Yuhe(Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院药物研究所,北京100050

出　　处：《中国药物警戒》2021年第4期315-319,共5页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金项目(81773925)。

摘　　要：目的探究帕金森病(Parkinson’s disease,PD)小鼠模型纹状体中多巴胺等神经递质的变化。方法通过腹腔注射丙磺舒(probenecid)、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转基因小鼠急性模型和野生型小鼠慢性模型;通过高效液相色谱法(high-performance liquid chromatography,HPLC)检测小鼠纹状体中神经递质的变化。结果HPLC结果显示,MPTP可以诱导野生型和A53T转基因小鼠纹状体中多巴胺(dopamine,DA)递质水平降低,二羟基苯乙酸(dihydroxyphenylacetic acid,DOPAC)水平降低,高香草酸(homovanillic acid,HVA)的水平降低,二羟基苯乙醛(dihydroxy phenylacetaldehyde,DOPAL)的含量升高,而对5-羟色胺(serotonin,5-HT)和去甲肾上腺素(norepinephrine,NE)无显著影响。结论MPTP诱导能够导致DA递质水平降低,以及其毒性代谢产物DOPAL含量增加,从而会促进PD的发生发展。Objective To explore the changes of such neurotransmitters as dopamine in the striatum of mouse models with Parkinson's disease(PD).Methods An acute PD model of A53T transgenic mice and a chronic PD model of wild-type mice were induced via intraperitoneal injection of probenecid and subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).High-performance liquid chromatography(HPLC)was used to detect the changes of neurotransmitters in the mouse striatum.Results HPLC results showed that MPTP could induce an decrease of dopamine(DA),dihydroxyphenylacetic acid(DOPAC),homovanillic acid(HVA)in the striatum,and an increase of dihydroxy phenylacetaldehyde(DOPAL).But the contents of serotonin(5-HT)and norepinephrine(NE)did not change significantly.Conclusion MPTP can induce a decrease in the level of DA transmitters and an increase in the content of its toxic metabolite DOPAL,thereby promoting the occurrence and development of PD.

关 键 词：帕金森病 1-甲基-4-苯基-1 2 3 6-四氢吡啶 纹状体 A53T 神经递质 

分 类 号：R994.1[医药卫生—毒理学]