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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C5 7BL 6小鼠腹腔注射MPTP4d制备PD模型 ,与MPTP同时给予莫达非尼 (ip ,5 0or10 0mg·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酪氨酸羟化酶 (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 ( 5 0和 10 0mg·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 .0 5和P <0 .0 1,n =10 ) ,阻止了MPTP造成的TH和尼氏体数量的减少 (P <0 .0 5 ,n =10 ) ,及纹状体中DA ,NA和 5 HT含量的降低 (P <0 .0 5 ,n =10 )。结论在MPTP诱导的PD小鼠模型中 ,莫达非尼可改善MPTP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。
Aim To observe the neuroprotective effect of modafinil on Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,6,6-tetrahydropyridine (MPTP) Methods The PD model was established by intraperitoneal injection of MPTP4d into C5 7BL 6 mice. After 4 days of modafinil with MPTP, the mice were treated with modafinil for 10 days. To observe the effects of modafinil on spontaneous activity, latent period of tremor, duration of maintenance, tremor score and pole-climbing time in mice, as well as tyrosine hydroxylase (TH) positive cells in striatum and substantia nigra The impact of the body. The contents of dopamine (DA), norepinephrine (NA) and serotonin (5 HT) in striatum were determined. Results Modafinil (50 and 100 mg · kg -1) significantly reduced spontaneous activity, tremor, and pole-climbing behavior in a dose-dependent manner (P <0.05 and P <0.01, n = 10) prevented the decrease of TH and the number of nissancies caused by MPTP (P <0.05, n = 10), and decreased the content of DA, NA and 5 HT in striatum (P <0.05 , n = 10). Conclusion In the MPTP-induced PD mouse model, modafinil can improve MPTP-induced behavioral defects of Parkinson’s disease and protect the monoamine neurons against injury.