脂多糖诱导黑质多巴胺能神经元变性中小胶质细胞的反应  

REACTION OF MICROGLIA IN LPS-MEDIATED SUBSTANTIA NIGRA DOPAMINERGIC DEGENERATION

作　　者：黎钢[1] 孙圣刚[1] 董大翠[2] 曹学兵[1] 胡波[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,武汉430022 [2]华中科技大学同济医学院解剖学系,武汉430030

出　　处：《中国组织化学与细胞化学杂志》2003年第3期250-254,共5页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金资助 (30 170 334) ;2 0 0 2年国家教委博士点基金资助 (2 0 0 2 0 4 870 6 5 )

摘　　要：目的　探讨小胶质细胞活化规律与脂多糖 (Lipopolysaccharide ,LPS)诱导黑质多巴胺 (DA)能神经元变性的关系。方法　脑立体定位注射LPS入大鼠脑黑质后 ,采用特异性抗体OX 4 2标记不同时间点小胶质细胞的激活情况 ;酪氨酸羟化酶 (tyrosine hydroxylase ,TH)免疫组织化学观察DA能神经元损害变化。结果　小胶质细胞在LPS注入黑质 6h后开始出现部分激活。 12h大部分激活 ,为“灌木丛样”小胶质细胞 ;2 4h已完全激活 ,呈现“阿米巴样” ,在随后的 30d内 ,基本维持在此形态。而TH阳性细胞数在第 3d开始出现下降 ,与对照组相比下降达 4 5 % ,14d时下降至 5～ 10 % ,至30d时几乎完全消失。结论　小胶质细胞的激活先于DA能神经元变性 ,其激活介导的炎症反应在PD发病中具有重要的神经破坏作用。Objective To explore the relationship between the pattern of activities of microglia and the degeneration effects of Lipopolysaccharide(LPS)on substantia nigra dopaminergic neurons.Method LPS was stereotaxically injected into substantia nigra (SN). Atdifferent survivaltimes, specific antibody OX-42 was used to detect the changes in morphology and the numbers of microglia; the damage to the substantia nigra DA neurons was observed by usingtyrosine-hydroxylase (TH) immunohistochemical staining. Result On the control side of the substantia nigra, all of the OX-42-positive microglia exhibited the typical ramified resting stage. 6h after injection of 5μg LPS into the rat SN, a portion of the OX-42-positive microglia started to be activated. At 12h post-injection most microglia were activated and appeared to be 'bushy'. At 24h, nearly all of the OX-42-positive microglia became fully activated with the characteristic 'amoeboid' morphology. In the subsequent 30 days, microglia remained at the stage of full activation. However, compared with the control groups, the number of TH positive neurons began to decrease to 45% onthe 3rd day after the injection, and the decrease was 5～10% on the 14th day and almost disappearedon the 30th day. Conclusion LPS-induced microglia activation precedes dopaminergic neuron degeneration;microglia activation-mediated inflammation plays a deleterious role in the pathogenesis of Parkinson disease.

关 键 词：脂多糖 小胶质细胞 活化规律 黑质多巴胺能神经元 炎症反应 

分 类 号：R338[医药卫生—人体生理学] Q421[医药卫生—基础医学]