首都医科大学学报 ›› 2003, Vol. 24 ›› Issue (3): 262-267.

• 论著·临床研究 • 上一篇    下一篇

α-Synuclein与帕金森病临床前期动物模型研究

邹春林1, 孙异临1, 曲宝清1, 盛树力2, 赵志炜2, 段春礼3   

  1. 1. 北京市神经外科研究所;2. 首都医科大学宣武医院;3. 首都医科大学北京神经科学研究所
  • 收稿日期:2002-12-17 修回日期:1900-01-01 出版日期:2003-07-15 发布日期:2003-07-15

On NACP and the preclinic animal model of Parkinson's Disease

Zou Chunlin1, Sun Yilin1, Qu Baoqing1, Sheng Shuli2, Zhao Zhiwei2, Duan Chunli3   

  1. 1. Beijing Neurosurgical Institute;2. Xuanwu Hospital, Affiliate of Capital University of Medical Sciences;3. Beijing Institute for Neuroscience, Capital University of Medical Sciences
  • Received:2002-12-17 Revised:1900-01-01 Online:2003-07-15 Published:2003-07-15

摘要: 用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)小剂量慢性给药建立帕金森病临床前期动物模型,观察小鼠脑组织形态学、生物化学及行为学方面的变化,同时对实验组小鼠黑质内α突触核蛋白(α-synuclein,NACP)阳性细胞数与纹状体内的突触数量进行动态变化的研究,探讨NACP与突触损伤之间的关系。C57BL/6j小鼠60只,根据给药时间长短分为5、10、15、20d 4组,腹腔注射MPTP〔4mg/(kg·d)〕,正常对照组注射生理盐水。最后一次给药后7d进行脑组织取材,分别进行NACP免疫组化染色、黑质纹状体形态学观察及纹状体内多巴胺含量的检测。发现:1)黑质内NACP免疫组化阳性细胞数在5d组为最高峰,随后各组逐渐减少。2)电镜下黑质内除见固缩的神经细胞外,其他的神经元也有超微病理改变如线粒体肿胀、粗面内质网减少等。3)各给药组小鼠纹状体内的多巴胺含量与正常对照组相比均有明显下降(P<0.01),各给药组之间无明显差异(P>0.05)。实验结果证实:1)低剂量MPTP慢性给药小鼠虽不能诱导出帕金森病的症状,但免疫组化、多巴胺含量测定及超微病理出现的改变可以作为帕金森病临床前期动物模型的参考指标。2)在MPTP慢性给药小鼠的早期阶段,黑质内神经细胞损伤时NACP表达水平增高可能是神经元本身对突触损伤的一种保护机制。

关键词: 帕金森病, 突触核蛋白, 动物模型

Abstract: The objective was to explore whether the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropydine (MPTP)-treated mice could be treated as the model of sporadic Parkinson's disease at preclinic stage by the research on the morphological, biochemical and behavioral changes of these mice brain, and to explore the relation between NACP and synaptic lesion during the early stage of Parkinson's disease by research on the relation between the alteration of the number of NACP-positive neurons and the alteration of the number of synapse of striatum in the chronic MPTP-treated mice model. Materials and Methods: C57BL/6j mice received intraperitioneal injection of MPTP4 mg/(kg·d)〕, and these mice were divided into four groups according to the days of MPTPinjection. The following tests were done: 1) Cryostat sections were studied by immunohistochemistry for NACP. 2) The morphmetric analysis of the striatum was done. 3) The neuropathological examination of the substantia nigra and the striatum was carried out. 4) Dopamine of the striatum was measured by HPLC-ECD, Western-blot. Results: 1) The number of NACP positive neurons in the substantia nigra reached a peak value in the 5-day group and gradually decreased after that time. 2) Electron microscopic results revealed that the number of synapse in the striatum decreased obviously in the 5-day group. 3) There was a significant difference (P<0.01)on content of DA in the striatum between the control and MPTP-treated groups, but there was no significant difference (P>0.05) between every MPTP-treated group. Conclusions: 1) The chronic MPTP-treated mice can be treated as the preclinic model of Parkinson's disease. 2) It is possible that the transitory increase in NACP in early stage of MPTP-treated mice model of PD might represent a compensatory mechanism to the ongoing synaptic damage.

Key words: Parkinson disease, NACP, animal model

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