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目的观察帕金森病小鼠模型黑质纹状体通路随病程进展而发生的形态学变化,从新的视角探讨帕金森病的病理生理机制。方法正常C57小鼠36只,随机分为生理盐水组和1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)组,每组18只,于注射后第7、14、21、25、28、35天取材,利用免疫组织化学、免疫荧光技术和激光扫描共焦显微镜观察黑质多巴胺能神经元的数量、在纹状体内投射的神经纤维密度及其在纹状体直接通路和间接通路神经元(D1R/D2R阳性神经元)上的分布比例。结果注射MPTP后,黑质多巴胺能神经元减少40%～50%;纹状体内多巴胺能神经纤维数量呈现先减少后增加的过程:第21天最少,仅为正常的20%;第35天最高,达到正常的45%;多巴胺能神经纤维在纹状体D1R/D2R阳性神经元上的分布比例也有先低后高的表现:第21天最低,第35天最高,与生理盐水组相比差异有显著性。结论 MPTP帕金森病模型小鼠的黑质纹状体通路呈现多巴胺能神经纤维再生现象,再生的多巴胺能神经纤维更多地分布于其直接通路的神经元上。
OBJECTIVE: To observe the morphological changes of nigrostriatal pathway in Parkinson’s disease mouse model and to explore the pathophysiological mechanism of Parkinson’s disease from a new perspective. Methods Thirty-six C57 mice were randomly divided into normal saline group and MPTP group (18 rats in each group) At days 7, 14, 21, 25, 28 and 35, the number of substantia nigra dopaminergic neurons, the density of neurons projected in the striatum and their effects on Distribution ratio of striatal direct and indirect pathway neurons (D1R / D2R positive neurons). Results After injection of MPTP, the number of substantia nigra dopaminergic neurons decreased by 40% -50%. The number of dopaminergic neurons in the striatum decreased first and then increased. The number of dopaminergic neurons in the striatum was at least 20% , Reaching 45% of the normal; dopaminergic nerve fibers in the striatum D1R / D2R-positive neurons distribution ratio also low first low after high performance: the lowest on the 21st day, the highest on the 35th day, compared with the saline group Significant. Conclusions The nigrostriatal pathway in mice with MPTP-induced Parkinson’s disease presents with regeneration of dopaminergic nerve fibers. The regenerated dopaminergic nerve fibers are more distributed in the neurons of their direct pathways.