莫达非尼对1-甲基-4苯基-1,2,3,6-四氢吡啶所致的帕金森病的神经保护作用

莫达非尼对1-甲基-4苯基-1,2,3,6-四氢吡啶所致的帕金森病的神经保护作用

肖艳丽^*, 董志, 傅洁民, 周岐新, 廖红

1.重庆医科大学药理教研室, 重庆 400016;
2.重庆医药工业研究院, 重庆 400061

收稿日期:2003-03-07 修回日期:2003-08-10 出版日期:2003-09-15 发布日期:2003-09-15
通讯作者: 肖艳丽*

Neuroprotective Effects of Modafinil on MPTP Mouse Model of Parkinson's Disease

XIAO Yan-li^*, DONG Zhi, FU Jie-min, ZHOU Qi-xin, LIAO Hong

1.Department of Pharmacology, Chongqing University of Medical Sciences, Chongqing 400016, China;
2.Chongqing Pharmaceutical Research Institute, Chongqing 400061, China

Received:2003-03-07 Revised:2003-08-10 Online:2003-09-15 Published:2003-09-15
Contact: XIAO Yan-li*

摘要/Abstract

摘要： 目的观察莫达非尼对1-甲基-4苯基-1, 2, 3, 6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型的神经保护作用. 方法给C57BL/6小鼠腹腔注射MPTP4d制备PD模型, 与MPTP同时给予莫达非尼(ip, 50 or 100mg·kg^-1·d^-1)4天后, 再连续给莫达非尼10天. 观测莫达非尼对小鼠的自发活动, 震颤潜伏期、维持期和震颤评分及爬杆时间的影响, 及对纹状体和黑质的酩氨酸羟化酶(TH)阳性细胞和尼氏体的影响.测定纹状体中多巴胺(DA), 去甲肾上腺素(NA)和5-羟色胺(5-HT)含量. 结果莫达非尼(50和100mg·kg^-1)呈剂量依赖性显著减少了自发活动、震颤和爬杆的行为缺陷(P<0.05和P<0.01, n=10), 阻止了MPTP造成的TH和尼氏体数量的减少(P<0.05, n=10), 及纹状体中DA, NA和5-HT含量的降低(P<0.05, n=10). 结论在MPTP诱导的PD小鼠模型中, 莫达非尼可改善MPMPTP引起的帕金森病行为缺陷, 且对单胺能神经细胞的损伤有保护作用.

关键词: MPTP, 帕金森病, 莫达非尼, 多巴胺, 酪氨酸羟化酶, 尼氏体

Abstract: Aim To observe the neuroprotective effects of modafinil on the Parkinson's disease ( PD ) model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Methods The model of PD was induced by intraperitoneal injection of MPTP into C57BL/6J mice for4 d. Modafinil (ip, 50 or 100 mg·kg^-1·d^-1) was administered following MPTP for 4 d and for another 10 d consecatirely. The effects of modafinil on the locomotor activity, and the incubation, maintenance period and grade of the tremor, the duration of the climbing rod of mouse, and the distribution of positive cells of tyrosine hydroxylase (TH) and Nissl bodies in the striatum and substantia nigra (SN) were observed. The contents of dopamine (DA) , noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in the striatum were determined. Results Modafinil (50 and 100 mg·kg^-1) significantly prevented the locomotor, the tremor and climbing rod defect behavior in a dose-dependent nanner (P<0.05 and P<0.01, n = 10), prevented the decrease in the number of TH-positive cells and Nissl bodies (P<0.05, n = 10), and reduced the decrease of DA, NA, and 5-HT in the striatum (P<0.05, n = 10) induced by MPTP. Conclusion Modafinil improves the behavioral deficits and prevents the monoaminergic neuron lesion in seriously impaired MPTP mouse model.

Key words: MPTP, MPTP, Parkinson's disease, Parkinson's disease, modafinil, modafinil, dopamine, dopamine, tyrosine hydroxylase, tyrosine hydroxylase, Nissl bodies, Nissl bodies

中图分类号:

R965

R971.5

Supporting: ^*Corresponding author. Tel.: 86-23-68486678

肖艳丽^*, 董志, 傅洁民, 周岐新, 廖红. 莫达非尼对1-甲基-4苯基-1,2,3,6-四氢吡啶所致的帕金森病的神经保护作用[J]. .

XIAO Yan-li^*, DONG Zhi, FU Jie-min, ZHOU Qi-xin, LIAO Hong. Neuroprotective Effects of Modafinil on MPTP Mouse Model of Parkinson's Disease[J]. .

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