目的 探讨Notch信号通路的缺失对1-甲基-4苯基-1,2,3,6-四氢吡啶（MPTP）诱导的中脑多巴胺能神经元损伤的影响。 方法 选用5月龄TH-Cre Rbpj基因敲除小鼠及野生型小鼠共48只，腹腔注射MPTP建立帕金森病（PD）模型，通过行为学、免疫组织化学和Western blotting等方法研究阻断Notch信号通路对MPTP诱导的中脑黑质多巴胺能神经元损伤的影响。 结果 MPTP处理的Rbpj CKO小鼠运动能力强于MPTP处理的野生型小鼠；Rbpj CKO小鼠黑质致密部神经元数目较野生型小鼠减少；MPTP处理后，野生型小鼠多巴胺能神经元数目明显下降，而Rbpj CKO小鼠多巴胺能神经元数目无明显改变；Western blotting结果显示，MPTP处理后Rbpj CKO小鼠和野生型小鼠Notch-1胞内结构域（NICD-1）的表达均明显增加，且Rbpj CKO小鼠表达量增加更为显著。 结论 Notch信号通路缺失导致多巴胺能神经元数量减少，阻断Notch信号通路可以降低MPTP诱导的多巴胺能神经元损伤。

Objective To investigate the impact of blocking of Notch signaling pathway (loss of expression of Notch signaling pathway) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage to midbrain dopaminergic neurons. Methods Both 5-month-old TH-Cre Rbpj gene knockout mice and wild type mice (n=48) were injected intraperitoneally with MPTP to produce a Parkinson’s disease (PD) animal model, then a variety of methods including behavioral test, immunohistochemistry and Western blotting were used to investigate the role of Notch signaling pathway in MPTP-induced loss of dopaminergic neurons in mouse midbrain. Results When treated with MPTP, Rbpj CKO mice exhibited better locomotor functions than wild type mice. Rbpj CKO mice were found to have fewer substantia nigra pars compacta (SNpc)neurons than wild type mice. After MPTP injection, the number of dopaminergic neurons were drastically reduced in wild type mice while in Rbpj CKO mice the number of these neurons remained virtually unchanged. Western blotting result showed that there was a significant increase in NICD-1 expression in both Rbpj CKO mice and wild-type mice, the increase was more profound in Rbpj CKO mice. Conclusion The deletion of Notch signaling pathway can lead to reduction in dopaminergic neurons, and deletion of Notch signaling pathway can reduce MPTP induced damage to dopaminergic neurons.