脑源性神经营养因子在脑室注射脂多糖大鼠黑质多巴胺能神经元变性中的作用

doi:10.3969/j.issn.1006-7795.2009.05.017

首都医科大学学报 ›› 2009, Vol. 30 ›› Issue (5): 648-652.doi: 10.3969/j.issn.1006-7795.2009.05.017

脑源性神经营养因子在脑室注射脂多糖大鼠黑质多巴胺能神经元变性中的作用

赵咏梅¹, 吕风月¹, 徐群渊²

1. 首都医科大学宣武医院神经变性病教育部重点实验室;2. 首都医科大学北京市神经科学研究所

收稿日期:2009-03-05 修回日期:1900-01-01 出版日期:2009-10-21 发布日期:2009-10-21

Effect of BDNF on Degeneration of Dopaminergic Neurons in the Substantia Nigra of a Model of Intra-ventricular Injection of Lipopolysaccharide in the Rat

ZHAO Yong-mei¹, LV Feng-yue¹, XU Qun-yuan²

1. Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Xuanwu Hospital, Capital Medical University;2. Beijing Institute for Neuroscience, Capital Medical University

Received:2009-03-05 Revised:1900-01-01 Online:2009-10-21 Published:2009-10-21

摘要/Abstract

摘要： 目的观察脑室内注射脂多糖(lipopolysaccharide,LPS)对大鼠黑质多巴胺能神经元的长时程毒性作用,探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)在黑质多巴胺能神经元慢性变性过程中的作用。方法健康雄性SD大鼠48只,采用抽签法将大鼠随机分为LPS实验组和0.9%氯化钠注射液(NS)对照组,经大鼠右侧脑室一次性注射LPS 20 μL(1.25 g/L)或0.9%氯化钠注射液20 μL。给药后2周、4周、12周、24周用酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组织化学染色观察黑质多巴胺能神经元的变化,免疫组化及酶联免疫吸附实验(enzyme immunoassay system,ELISA)检测黑质纹状体系统BDNF表达的变化。结果 1 TH免疫组织化学染色结果显示,大鼠黑质多巴胺能神经元数目在LPS给药后期减少,24周时LPS实验组大鼠黑质TH阳性神经元数量为NS对照组的75.4％(P<0.01);2 BDNF免疫组化结果显示,LPS实验组大鼠4周时黑质部位BDNF阳性细胞的表达较NS对照组高,而到12周和24周时其表达比NS对照组明显下降。ELISA检测结果显示,LPS实验组大鼠4周时黑质纹状体内BDNF表达是NS对照组的186.3%(P<0.01),而12周和24周时分别是NS对照组的42.3%(P<0.01)和61.0%(P<0.05)。结论脑室内注射LPS可导致大鼠黑质多巴胺能神经元变性,这一病变过程呈慢性迟发性。该模型大鼠黑质TH阳性神经元变性丢失前即出现黑质纹状体系统BDNF表达减少,提示BDNF表达减少可能是黑质多巴胺能神经元变性丢失的原因之一。

关键词: 脑源性神经营养因子, 多巴胺能神经元, 变性, 脂多糖, 大鼠

Abstract: Objective To investigate neurotoxic effects of intra-ventricularly injected lipopolysaccharide(LPS) on dopaminergic(DA) neurons in the substantia nigra and to explore the role of brain-derived neurotrophic factor(BDNF) in the long-term degeneration of dopaminergic neurons in rats. Methods Altogether 48 healthy male SD rats were assigned into LPS-injected group and saline-injected group randomly. All injections were made intra-ventricularly on right side with LPS 20 μL(1.25 g/L)or saline 20 μL. The changes of dopaminergic neurons in the substantia nigra were studied by using tyrosine-hydroxylase(TH) immunohistochemical staining. The changes of BDNF were detected by immunohistochemical staining and enzyme immunoassay system(ELISA). Results The number of TH-positive neurons in the substantia nigra in LPS-injected rats decreased at 24 weeks after LPS injection. The number of TH-positive neurons in LPS-injected group was 75.4% of that in saline-injected group(P<0.01). The BDNF-positive cells in the substantia nigra in LPS-injected group increased markedly compared with saline-injected group at 4 weeks, while at 12 weeks and 24 weeks, the BDNF-positive cells in the substantia nigra in LPS-injected group decreased obviously compared with those in saline-injected group. The results of ELISA showed that BDNF protein levels in LPS-injected group were 186.3% of those of saline-injected group at 4 weeks(P<0.01). While at 12 weeks and 24 weeks post LPS injection, BDNF protein levels in the substantia nigra and corpus striatum of LPS-injected group were 42.3%(P<0.01) and 61.0%(P<0.05) of those in saline-injected group, respectively. Conclusion A single intra-ventricular administration of LPS in rats may result in a significant and a delayed loss of dopaminergic neurons in the substantia nigra. After LPS injection, a decrease of BDNF protein level in the substantia nigra occurs before the degeneration of dopaminergic neurons, suggesting that the decrease of BDNF may be one of the reasons that induced the loss of dopaminergic neurons induced by cerebral inflammation.

Key words: brain-derived neurotrophic factor, dopaminergic neurons, degeneration, lipopolysaccharide, rat

中图分类号:

赵咏梅;吕风月;徐群渊. 脑源性神经营养因子在脑室注射脂多糖大鼠黑质多巴胺能神经元变性中的作用[J]. 首都医科大学学报, 2009, 30(5): 648-652.

ZHAO Yong-mei;LV Feng-yue;XU Qun-yuan. Effect of BDNF on Degeneration of Dopaminergic Neurons in the Substantia Nigra of a Model of Intra-ventricular Injection of Lipopolysaccharide in the Rat[J]. Journal of Capital Medical University, 2009, 30(5): 648-652.

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脑源性神经营养因子在脑室注射脂多糖大鼠黑质多巴胺能神经元变性中的作用

Effect of BDNF on Degeneration of Dopaminergic Neurons in the Substantia Nigra of a Model of Intra-ventricular Injection of Lipopolysaccharide in the Rat

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