基础医学与临床 ›› 2008, Vol. 28 ›› Issue (7): 747-751.

• 研究论文 • 上一篇    下一篇

LPS致大鼠黑质多巴胺能神经元及血清TNF-α变化的研究

张莉 王彦永 崔冬生 顾平 王铭维   

  1. 河北医科大学;河北医科大学第一医院 河北医科大学第一医院 河北医科大学第一医院 河北医科大学第一医院 河北医科大学第一医院神经内科
  • 收稿日期:2007-04-11 修回日期:2007-10-08 出版日期:2008-07-25 发布日期:2008-07-25
  • 通讯作者: 张莉

Changes of Substantia Nigral Dopaminergic Neurons and TNF-α in Serum Induced by LPS

Li ZHANG, Yan-yong WANG, Dong-sheng CUI, Ming-wei WANG   

  • Received:2007-04-11 Revised:2007-10-08 Online:2008-07-25 Published:2008-07-25
  • Contact: Li ZHANG,

摘要: 目的 研究脂多糖(Lipopolysaccharide,LPS)对黑质多巴胺(DA)能神经元的毁损情况及其与血清肿瘤坏死因子α(TNF-α)水平之间的关系。方法 向大鼠右侧黑质立体定位注射LPS或PBS后,用免疫组化法观察黑质DA 能神经元的损伤状况,用放射免疫法测定血清TNF-α水平。结果 LPS 注射后24h右侧黑质酪氨酸羟化酶(Tyrosine-hydroxylase,TH)阳性神经元较左侧显著减少,14d达到高峰,此后至28d没有明显改变;和PBS组大鼠血清TNF-α水平相比较,24h、14d、28d的显著增高;LPS组大鼠的黑质TH 阳性神经元存留率与其血清TNF-α水平之间存在负直线相关关系。结论LPS诱导的DA能神经元毁损短期内呈时间依赖性,其破坏作用只是阶段性的;帕金森病(PD)发病中黑质局部的炎症反应可以引起全身的炎症反应;血清TNF-α水平与黑质DA能神经元变性、死亡密切相关。

关键词: 帕金森病, 脂多糖, 多巴胺能神经元, 肿瘤坏死因子α, 炎症

Abstract: Objective To study the degeneration of dopaminergic neurons and the relationship between it and the level of TNF-α in serum by intranigral injection of LPS. Methods LPS or PBS was stereotaxically injected into substantia nigra(SN).At different survival times,the damage to the substantia nigral DA neurons was observed by using tyrosine-hydroxylase immunohistochemical staining and the level of TNF-α in serum was measured by Radioimmunoassay. Results 24 hours after LPS injection,there was apparent reduction in TH-positive cells on the LPS-injected side.The decrease reached a peak after 14 days.In the subsequent days,the degree of degeneration remained at the stage. Differences were observable when compared the level of TNF-α in serum of 24h、14d、28d with that of the PBS group.The former was higher. The study revealed linear correlation between the level of TNF-α and the survival rate (percentage of right TH-positive neurons to left). Conclusion The degeneration of TH-positive neurons induced by inflammation was in time-dependent manner. While in development of PD the effect of inflammatory damage was only early stage;In PD local inflammation in substantia nigra may be induce systemic inflammatory reaction; The level of TNF-α in serum is related to the degeneration of TH-positive neurons in substantia nigra.

Key words: Parkinson Disease, Lipopolysaccharide, dopaminergic neuron, tumour necrosis factor-α, inflammation