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山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (2): 52-57.

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noggin对帕金森病大鼠黑质神经元的保护作用

朱俊德,余资江,戈果   

  1. 贵阳医学院基础医学院人体解剖学教研室, 贵阳  550004
  • 收稿日期:2009-09-17 出版日期:2010-02-16 发布日期:2010-02-16
  • 通讯作者: 余资江(1968- ),教授,主要从事神经损伤与修复的研究。
  • 作者简介:朱俊德(1973- ),讲师,硕士,主要从事神经损伤与修复的研究。E-mail: zjd@gmc.edu.cn
  • 基金资助:

    国家自然科学基金资助项目(30660189);贵阳医学院博士启动基金资助项目(C2006-4);2009年度贵州省社会发展科技攻关计划项目[黔科合SY字(2009)3058];贵阳医学院青年教师基金资助项目(K2007-61、63)

Protective effects of noggin on substantia nigra neurons in Parkinson′s disease model rats

ZHU Junde, YU Zijiang, GE Guo   

  1. Department of Anatomy, School of Basic Medicine, Guiyang Medical University, Guiyang 550004, China
  • Received:2009-09-17 Online:2010-02-16 Published:2010-02-16

摘要:

目的  观察noggin对6-羟基多巴胺(6-OHDA)致帕金森病模型大鼠神经行为的影响及其对黑质神经元的保护作用。方法  随机将60只雄性SD大鼠,分为正常对照组、模型组和模型治疗组。采用脑立体定位右侧纹状体内注射6-OHDA构建帕金森病(PD)模型,模型治疗组纹状体内注射noggin,正常对照组与模型组同时给予等量生理盐水,术后7d于行为检测完毕后行尼氏染色、TH、TUNEL与GFAP免疫组化染色,光镜下观察3组大鼠黑质多巴胺能神经元、凋亡神经元与星形胶质细胞的形态变化并进行计量分析,电镜下观察黑质神经元超微结构变化。结果    模型治疗组大鼠的旋转次数较模型组明显改善(P<0.05),TH阳性神经元较模型组增多,凋亡神经元显著减少(P<0.05),GFAP阳性神经元较模型组减少,胞浆内GFAP阳性产物的平均光密度值亦明显降低(P<0.05);TH、TUNEL与GFAP阳性神经元主要位于黑质致密部;电镜下对照组黑质神经元结构清晰,胞核形态规则,核膜光滑、完整,染色质分布均匀;胞浆电子密度中等,细胞器丰富;模型组黑质神经元胞核皱缩,核膜凸凹不整、异染色质减少,胞浆内大量线粒体嵴断裂消失,粗面内质网扩张;模型治疗组黑质神经元细胞核形态规则,部分线粒体肿胀,细胞器丰富。结论  noggin可改善PD模型大鼠的行为能力、使凋亡神经元及反应性星形胶质细胞数目减少,这些变化可能与noggin能促进黑质内部分神经元再生有关。

关键词: 多巴胺;帕金森病;黑质;神经元;大鼠;noggin

Abstract:

Objective  To study the behavioral abilities and morphological changes on neurons of substantia nigra of Parkinson′s disease(PD) model rats induced by 6hydroxydopamine(6-OHDA) and observe the effect of the AdTrack-CMV-noggin plasmid on the PD model rats. Methods  Sixty mature Sprague-Dawley male rats were randomly divided into the normal control group, the model group and the noggin treatment group. The PD rat model was established by microinjection of 6-OHDA solution into the right corpus striatum. The AdTrack-CMV-noggin plasmid was injected into the same area after two days in the noggin treatment group, and an identical volume of saline was given to the model group and the normal control group. The behavior of rats was detected by QL-small animal revolved apparatus after seven days. Then, TH, TUNEL-and GFAP-immunopositive neurons in the SN were observed under a light microscope, and quantitative analysis was performed by cell morphometric technique. The ultra-microstructure of the neurons was observed by a transmission electron microscope (TEM).  Results  Rotational behavior of the noggin treatment  rats was significantly improved in comparison with those of the model rats (P<0.05). The quantity of TH-positive cells was increased in the noggin treatment group;however, apoptosis cells were significantly decreased (P<0.05). The quantity  and average optical density of GFAPpositive cells were significantly decreased (P<0.05). TH, TUNEL-and GFAP-immunopositive neurons were mainly in the substantia nigra compacta (SNc). Under TEM, moderate electron-density cytoplasm, regular nuclei, complete perinuclear membrane, evenly distributed chromatin and abundant cell organelles in the SN neurons were shown in the normal group; while shrunken nuclei, irregular perinuclear membrane, decreased heterochromatin, collapsed mitochondria cristae, and distended rough endoplasmic reticulum were shown in the model group. Neurons of the noggin treatment group were improved compared with those of the model group, some of which had distinct structure and abundant cell organelles. Conclusion  6-OHDA induces the impairment of neurogenesis in the PD model rats. Noggin could effectively improve the behavior of the PD model rats and decrease the quantity of apoptosis cells and astrocytes, which might be related to promoting neurogenesis in some parts of the SN.

Key words: Dopamine; Parkinson disease; Substantia nigra; Neurons; Rats; Noggin

中图分类号: 

  • R338.1
[1] 蒋鸫,康朝胜,杨向斌 . 慢性铝中毒对大鼠海马CA3区神经胶质细胞的影响[J]. 山东大学学报(医学版), 2011, 49(6): 20-23.
[2] . Noggin蛋白对D半乳糖致衰老小鼠学习记忆及海马齿状回神经发生的影响[J]. 山东大学学报(医学版), 2009, 47(8): 72-74.
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