脂多糖对大鼠黑质纹状体多巴胺能系统的影响  

Influence of Intranigral Injection of Lipopolysaccharide on the System of Substantia Nigral and Striatum in Rats

作　　者：黎钢[1] 孙圣刚[1] 马嵘[2] 曹学兵[1] 肖伟忠[1] 袁光雷[1] 徐岩[1] 童萼塘[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经科,湖北武汉430022 [2]华中科技大学同济医学院药理学系,湖北武汉430030

出　　处：《中国神经免疫学和神经病学杂志》2005年第1期1-5,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目(30170334);2002年国家教委博士点基金资助项目(20020487065)

摘　　要：目的观察脂多糖(lipopolysaccharide ,LPS)对大鼠黑质纹状体系统的神经毒性作用,探讨帕金森病(Parkinson disease,PD)与炎症反应的关系. 方法采用立体定向术向大鼠脑黑质注射5 μg LPS,于注射后不同时间点(1、3、7、14、21、30 d)观察经腹腔注射阿朴吗啡后大鼠的旋转行为以及采用高效液相色谱(HPLC)测定黑质-纹状体单胺类递质含量的变化;通过免疫组化观察多巴胺(dopamine,DA)合成限速酶酪氨酸羟化酶(tyrosine-hydroxylase,TH)的变化.结果 LPS注射后14、21、30 d大鼠出现向注射侧的旋转行为,黑质-纹状体DA及其代谢产物随时间延长呈不同程度下降(P＜0.05),而5-羟色胺(5-HT)仅有短暂下降,去甲肾上腺素(noradrenaline,NA)无变化.TH阳性细胞数在第3天开始下降为对照组的45%,14 d时为对照组的5%～10%,30 d时几乎完全消失.结论 LPS注射黑质后能特异性损害DA能神经元,可用于建立PD免疫炎症动物模型.Objective To investigate the neurotoxicity of lipopolysaccharide (LPS )on substantia nigra (SN)and striatal system of rats and explore the relation between Parkinson disease (PD) and inflammatory reaction.Methods LPS was stereotaxically infused into SN of rats. At different survival times, rotation test induced by apomorphine were performed in all groups after LPS injection. The levels of monoamine transmitters in the nigrostriatal system were measured by using HPLC-ECD; The damage of the SN DA neurons was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining . Results 14,21,30 d after injection of 5 μg LPS into the rat SN, the rotational behaviors induced by apomorphine were observed. The levels of DA and their metabolites in the SN and striatum were decreased, while the levels of 5-HT in the SN and striatum were transient changed and the levels of noradrenaline showed no change.As compared with the control groups, TH positive neurons began to decrease at 3 d and obviously decreased at 14 d, only 5% of total cells, were almost disappeared at 30 d later. Conclusions LPS mainly affects the dopaminergic system to reduce the DA and their metabolites in the nigrostriatal, and maybe an useful tool to establish PD model.

关 键 词：帕金森病 脂多糖 炎症反应 

分 类 号：R742.5[医药卫生—神经病学与精神病学]