大鼠脑内炎症对黑质多巴胺能神经元的长时程毒性作用及星形胶质细胞变化  

Long-term neurotoxic effect of intracephalic inflammation on substantia nigra dopaminergic neurons and the changes of asctrocytes in rats

作　　者：赵咏梅[1] 吕风月[1] 许秋岩[1] 闫颖[1] 徐群渊[2] 

机构地区：[1]首都医科大学宣武医院神经变性病教育部重点实验室,北京100053 [2]首都医科大学北京神经科学研究所

出　　处：《中华老年医学杂志》2010年第5期416-419,共4页Chinese Journal of Geriatrics

基　　金：基金项目：国家重点基础研究发展计划（2006CB500700）;教育部留学回国人员科研启动基金

摘　　要：目的探讨侧脑室注射脂多糖（lipopolysaccharide）引发大鼠脑内炎症时，星形胶质细胞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60只，随机分为脂多糖实验组和生理盐水对照组。向大鼠右侧脑室内一次性注射脂多糖或生理盐水，于不同时间点检测大鼠运动行为变化；用免疫组织化学染色方法检测大鼠黑质部位胶质纤维酸性蛋白（glial fibrillary acid protein，GFAP）的表达，观察星形胶质细胞的激活情况。结果脂多糖实验组大鼠30min运动距离在给药后16周较相应生理盐水对照组降低21．2％（t=2．54，P〈0．05），给药后24周降低27．0％（t=3．55，P〈0．01），28周降低31．4％（t=3．91，P〈0．01）。脂多糖实验组大鼠给药后2周，黑质部位星形胶质细胞明显激活，GFAP阳性细胞数目[（228．60±22．35）个]较相应生理盐水对照组[（165．20±25．97）个]明显增加（t=4．14，P〈0．05）。4周及12周时实验组大鼠黑质部位星形胶质细胞激活不明显。给药后24周，实验组大鼠黑质部位星形胶质细胞又明显激活，GFAP阳性细胞数目（（220．00±21．01）个]较相应生理盐水对照组[（169．00±19．00）个]明显增加（t=4．03，P〈0．05）。生理盐水对照组大鼠黑质部位星形胶质细胞在注射后各时间点均未见明显激活。结论在脑内炎症导致的大鼠黑质多巴胺能神经元慢性变性过程中，星形胶质细胞呈现“急性激活一静止一再次激活”状态。星形胶质细胞在黑质多巴胺能神经元变性中发挥了一定作用。Objective To investigate the role of asctrocytes in the process of chronic degeneration of dopaminergic neurons in intracephalic inflammation rat model induced by intracerebroventricularly injection of lipopolysaccharide. Methods Sixty healthy male SD rats were assigned into lipopolysaccharide group or saline control group randomly. All injections were made intracerebroventricularly on right side of the rats. Ethovison software was used to measure the movement distance of rats within 30 minutes. Specific antibody for glial fibrillary acid protein （GFAP） was used in immunohistochemistry stain to detect the changes of asetrocytes in the substantia nigra of rats. Results Movement distance of lipopolysaccharide-injected rats decreased by 21.2% compared with saline-injected rats at 16 weeks after injection （t=2.54, P〈0.05）by 27.0% （t=3.55, P〈 0.01） at 24 weeks and by 31.4% （t=3.91, P〈0.01） at 28 weeks after lipopolysaccharide injection. The asctrocytes were activated obviously in the substantia nigra of lipopolysaccharide-injected group at 2 weeks,while the numbers of GFAP-positively stained cells （228.60± 22.35） increased significantly compared with saline-injected group （ 165.20 ± 25.97） （t = 4.14, P 〈 0.05）. The activation of asctrocytes was not found in lipopolysaccharide-injected group at 4 weeks and 12 weeks. The asctrocytes were re-activated in the substantia nigra of lipopolysaccharide-injected group at 24 weeks, while the numbers of GFAP-positively stained cells （220.00 ± 21.01） increased significantly compared with saline-injected group （169. 00±19.00） （t=4.03, P〈0.05）. The activation of asctrocytes was not seen at any time point in saline-iniected group. Conclusions Intracephalic inflammation induces chronic degeneration of substantia nigral dopaminergic neurons in rats. The asctrocytes exhibite ＂acute activation-quiescing-reactivation＂ state, indicating that they might be involved in the mechanism of dopaminergic neurons degeneration.

关 键 词：帕金森病 神经胶质 炎症 黑质 多巴胺 

分 类 号：R742.5[医药卫生—神经病学与精神病学]