脑内炎症反应对大鼠黑质多巴胺能神经元长时程毒性作用的研究  

THE LONG-TERM NEUROTOXIC EFFECT OF INFLAMMATION ON DOPAMINERGIC NEURONS IN RAT SUBSTANTIA NIGRA

作　　者：李军泉[1] 王元身[1] 孙晓红[1] 张进禄[1] 徐群渊[1] 

机构地区：[1]首都医科大学北京神经科学研究所,北京市神经再生修复研究重点实验室,教育部神经变性病学重点实验室,北京100069

出　　处：《解剖学报》2008年第3期350-354,共5页Acta Anatomica Sinica

基　　金：国家重点基础研究发展计划(973)(2006CB500700;2007CB947704);国家自然科学基金重点项目(30430280);教育部博士学科点专项科研基金(20040025007);北京市科技计划基础研究专项(Z0005187040311)资助

摘　　要：目的观察黑质部位炎症反应对多巴胺能神经元的长时程毒性作用,探讨脑内炎症反应在黑质多巴胺能神经元慢性变性过程中的作用。方法健康SD雄性大鼠28只,随机分为生理盐水组和10μg、25μg、50μg脂多糖组。定位注射生理盐水或脂多糖入右侧脑室,术后24周观察大鼠行为学改变,免疫组织化学染色观察黑质部位小胶质细胞的激活情况及酪氨酸羟化酶阳性神经元的变化。结果1.大鼠行为学观察显示,10μg、25μg和50μg脂多糖组大鼠的平均运动速度与对照组相比,差异无统计学意义。2.OX-42免疫组织化学染色显示,10μg和25μg脂多糖组大鼠黑质部位小胶质细胞激活明显。50μg脂多糖组大鼠黑质部位小胶质细胞激活不明显。3.酪氨酸羟化酶免疫组织化学染色显示,10μg和25μg脂多糖组大鼠黑质酪氨酸羟化酶阳性神经元与对照组相比,胞体变小,突起减少甚至消失,染色变浅;50μg脂多糖组大鼠酪氨酸羟化酶阳性神经元形态与对照组相比没有明显改变。4.酪氨酸羟化酶阳性细胞计数显示,10μg和25μg脂多糖组大鼠与对照组比较,分别减少15.5%(P<0.01)和20.1%(P<0.01);50μg脂多糖组大鼠与对照组比较没有统计学差异。结论脑室注射脂多糖引发的脑内炎症可导致黑质多巴胺能神经元变性,这一过程呈慢性迟发性;同时,低剂量脂多糖激活小胶质细胞对黑质多巴胺能神经元的慢性毒性作用更为明显;该病理过程较好地模拟了帕金森病的发病特点。Objective To investigate the long-term neurotoxic effect of inflammation induced by intracerebroventricular injection of lipopolysaeeharide （LPS） on dopaminergie neurons in the substantia nigra of rats, in order to explore the mechanism of inflammation in the progressive nature of Parkinson＇ s disease. Methods 28 healthy male SD rats were randomly assigned to 10μg, 25μg, 50μg LPS-injeeted groups and saline-injected group. All injections were made intraeerebroventrieularly on the right side with LPS or saline. Moving distance and speed were measured by Ethovison software. Tyrosine hydroxylase （TH）-positive neurons and mieroglia were demonstrated by immunohistoehemistry staining. Results Analysis of moving speed showed no significant difference between groups with 10μg, 25μg, 50μg of LPS and saline injections. The mieroglia were activated mostly in the brain in 10μg and 25μg LPS-injeetion groups, while the activation of mieroglia was not found in 50μg LPS- and saline-injected rats. The TH-positive neurons in the substantia nigra of 10μg and 25μg LPS-injeeted groups decreased by 15.5 % （ P 〈 0.01 ） and 20.1% （P 〈 0.01 ） respectively, compared with those in the saline-injected group, but there was no significant difference between 50μg LPS- and saline-injected groups. Conclusion Single intraeerebroventrieular administration of LPS with a lower dosage may result in a significant and delayed loss of dopaminergie neurons in the substantia nigra, indicating that the reactive mieroglia induced by inflammation plays an important role in the long-term degeneration of dopaminergie neurons.

关 键 词：帕金森病 脂多糖 小胶质细胞 酪氨酸羟化酶 免疫组织化学 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]