黑质内注射脂多糖对多巴胺能神经元和小胶质细胞活性的影响  

Effects of Nigral Lipopolysaccharide Administration on Dopaminergic neural Dysfunction and Glial Cell Activation

作　　者：王普清[1] 孙圣刚[1] 张允健[1] 乔娴[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,武汉430022

出　　处：《中国康复》2008年第6期380-382,共3页Chinese Journal of Rehabilitation

摘　　要：目的:观察脂多糖(LPS)对黑质多巴胺能神经元的损毁作用以及对小胶质细胞活性的影响。方法:60只雌性SD大鼠随机分为正常组、1d组、1周组、2周组和2个月组各12只,除正常组外,其余各组采用立体定向技术向大鼠单侧黑质内注入LPS,于注药后1d、1周、2周和2个月时分别经腹腔注射阿朴吗啡诱发动物旋转行为为造模成功;按各组不同时间点观察大鼠黑质酪氨酸羟化酶(TH)阳性细胞数变化和小胶质细胞活化过程、纹状体和黑质部位多巴胺(DA)及其代谢产物含量及黑质变性神经元。结果:单侧黑质内注入LPS后的各组黑质TH+细胞数分别较对侧减少12%～71.5%;其损伤侧纹状体和黑质DA及其代谢物含量降低28.2%～65.7%(均P<0.05～0.01);1周组Fluoro-JadeB染色可见染色阳性神经元;LPS注射的各组黑质均可见活化的小胶质细胞。结论:黑质注入LPS可诱导小胶质细胞活化和黑质多巴胺能神经元变性死亡。Objective： To investigate the effects of nigral lipopolysaccharide （LPS） administration on dopaminer gic neural dysfunction and glial cell activation. Methods： Sixty female SD rats were randomly divided into 5 groups： control, 1-day, 1 week, 2 week and 2 month. LPS was stereostatically injected into unilateral substantia nigra of rats except control group. At different survival time points, circling behavior was observed by intraperitoneal injection of Apo morphine during the intervals of 1 week to 2 months after injection. The damage to the substantia nigra DA neurons was observed by tyrosine-hydroxylase （TH） immunohistochemical staining. Specific antibody OX-42 was used to detect the changes in morphology and the number of microglia. Immunohistochemistry was used to detect midbrain dopaminergic neurons and microglia. The contents of monoamine in the nigrostriatal system were measured by high performance liquid chromatography （HPLC）. The degenerative neurons in the substantia nigra were detected by Fluoro-JadeB staining. Results： Compared with the control group, the 12% to 71.5% reduction of TH-positive cells in the lesion of substantia nigra was found in 1-day, 1-week, 2-week and 2-month groups after LPS treatment. Com- pared with the control group, the 28.2% -65.7% reduction of dopamine and its metabolite （DOPAC） in the lesion of striatum and substantia nigra was found in 1-day, 1-week, 2-week and 2-month groups. The activation of microglia was also observed from 24 h to 2 months after LPS treatment. There were a number of the positive degenerative neu- rons in the substantia nigra. Conclusion： LPS intranigral injection could induce the activation of microglia and the degeneration of dopaminergic neurons in the substantia nigra.

关 键 词：帕金森病 脂多糖 多巴胺能神经元 小胶质细胞 

分 类 号：R742.5[医药卫生—神经病学与精神病学]