星形胶质细胞参与脑内炎症致大鼠多巴胺能神经元变性  

Astrocytes involve in the degeneration of dopaminergic neurons induced by intracephalic inflammation in rat

作　　者：吕风月[1] 赵咏梅[1] 李军泉 徐群渊 

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]北京市神经科学研究所

出　　处：《中华行为医学与脑科学杂志》2009年第1期13-15,共3页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金资助项目（30670656）;国家“973”重点基础研究发展计划（2007CB947704）;教育部留学回国人员科研启动基金

摘　　要：目的观察脑室内注射脂多糖（lipopolysaccharide，LPS）引起的脑内炎症对大鼠黑质多巴胺能神经元的慢性毒性作用，探讨星形胶质细胞是否参与脑内炎症致大鼠多巴胺能神经元变性。方法60只SD大鼠分为LPS实验组和生理盐水（NS）对照组（n=30）。大鼠右侧脑室一次性注射LPS 20μl（i．25μg／μl）或同体积的NS。于给药后不同时间检测大鼠行为，免疫组织化学染色法观察黑质内酪氨酸羟化酶（TH）阳性神经元，并用Western blot检测大鼠黑质纹状内胶质纤维酸性蛋白（GFAP）的表达。结果1）LPS给药后大鼠平均运动速度呈进行性下降，与相应NS对照组相比，在16周[（2．12±0．43）cm/s，（1．67±0．36）cm／s，t：2．537，P〈0．05]、20周[（2．03±0．31）cm／s，（1．46±0．33）cm／s，t=3．981，P〈0．01]和24周[（2．00±0．36）cm／s，（1．46±0．32）ctn,／s，t=3．545，P〈0．01]均差异有显著性。LPS给药后大鼠黑质TH阳性神经元数量减少，在24周时是相应NS对照组的75．4％（P〈0．01）。2）LPS实验组大鼠给药后2周时，黑质纹状体部位GFAP蛋白表达量比相应NS对照组明显增高，为NS对照组的258％（P〈0．01）。到给药后24周时，LPS实验组大鼠黑质纹状体内GFAP蛋白表达量又比NS对照组明显增高，为NS对照组的168％（P〈0.05）。结论侧脑室注射LPS引发大鼠黑质部位星形胶质细胞激活，参与了黑质多巴胺能神经元的变性过程。Objective To investigate the role of astrocytes in the process of long-term degeneration of dopaminergic neurons in inflammation rat model induced by intracerebroventricular injection of lipopolysaccharide （LPS）. Methods Altogether 60 SD rats were assigned into LPS group（ n = 30） or saline control group（ n = 30）. All injections were made intracerebroventricularly on right side of the rats with LPS 20 μl（ 1.25 μg/μl） or saline 20 μl. After injection, movement speed of rats was measured,and the changes of substantia nigra dopaminergic neurons were observed by using tyrosine-hydroxylase （TH） immunohistochemical staining. Western blot was performed to detect GFAP expression in rat substantia nigra and corpus striatum. Results 1 ） Intracerebroventricular injection of LPS induced dopaminergic neurons degeneration in rat. Movement mean speed of LPS-treated rats decreased significantly compared with those of saline-treated rats at 16 weeks [ （2.12 ±0. 43 ）cm/s vs （1.67 ± 0.36 ）cm/s, t = 2. 537 , P 〈 0. 05 ] ,20 weeks [（2.03±0.31）cm/s vs （1.46 ±0.33） cm/s,t =3.981,P〈0.01] and 24 weeks [ （2.00 ±0.36） cm/s vs （ 1.46 ±0.32 ） cm/s, t = 3. 545, P 〈 0.01 ] post injection. The number of TH- positive neurons in the substantia nigra of LPS-injected rats decreased after LPS injection. TH-positive neurons in LPS-injected rats were 75.4% of those of saline-injected group at 24 weeks （ P 〈 0.01 ）. 2） The expression of GFAP in substantia nigra and corpus striatum in LPS-injected group was 258% of that of saline control group at 2 weeks（P〈0. 01 ） ,the expression of GFAP in LPS-injected group was 168% of saline control group at 24 weeks（P 〈 0. 05）. Conclusion A single intracerebroventricular administration of LPS may result in the activation of astrocytes in the substantia nigra in rat, which may involve in the degeneration process of dopaminergic neurons.

关 键 词：炎症 脂多糖 黑质 多巴胺能神经元 星形胶质细胞 

分 类 号：R686[医药卫生—骨科学]