Minocycline对Lactacystin大鼠模型黑质胶质活化和多巴胺神经元生存的干预作用  

Intervention effects of minocycline on nigral glial activation and of dopamine neuronal survival in the lactacystin rat model of Parkinson's disease

作　　者：焦西英[1] 孙晓龙[1] 段丽[1] 夏毅[1] 张磊[1] 陈良为[1] 

机构地区：[1]第四军医大学全军神经科学研究所,西安710032

出　　处：《神经解剖学杂志》2013年第2期127-132,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81071609);973项目(2011CB504103)

摘　　要：目的:观察米诺环素(Minocycline,Mino)对Lactacystin(Lac)模型黑质内胶质细胞反应和多巴胺神经元的干预作用。方法:成年SD大鼠30只随机分为对照、Lac1 W、Lac3 W、Lac5 W、Lac+Mino5 W组,进行Lac动物模型制备和Mino给药处理,通过免疫组织化学和Western blot方法,观察iba1(小胶质细胞标志物)、GFAP(星形胶质细胞标志物)、TH(多巴胺能神经元标志物)的表达水平或阳性细胞数量变化,分析评价黑质内胶质细胞反应和多巴胺神经元生存状态。结果:Lac处理模型黑质内胶质细胞呈现动态活化反应。与生理盐水对照组相比,Lac处理均诱导iba1和GFAP表达水平升高,iba1在Lac3 W组显著升高、并持续高水平至Lac5 W(P<0.05)。GFAP表达在Lac1 W已显著升高、维持至Lac3 W和Lac5 W(P<0.05)。伴随胶质细胞的显著活化反应,黑质内TH阳性神经元数量急剧减少(P<0.01)。与Lac5 W组相比,Lac+Mino5 W组呈现对iba1和GFAP阳性胶质细胞的抑制效应、并提高黑质内TH阳性细胞数量,具有统计学意义(P<0.05)。结论:小胶质细胞抑制剂米诺环素给药处理可能通过干扰胶质细胞的异常活化反应、发挥对Lac损伤模型黒质多巴胺能神经元的一定保护作用。Objective： To investigate intervention effect of Minocycline （Mino） on nigral glial activation and dopamine neuronal survival in the lactacystin （Lac） rat model. Methods： Male adult SD rats （n = 30） were randomly divided into control, Lacl W, Lac3 W, Lac5 W, and Lac ＋ MinoSW group. The lactacystin animal model was prepared and Minocyline was administrated afterwards. Western blotting and immunohistochemistry for ionized calcium binding adaptor mole- cule 1 （ ibal ）, Glial fibrillary acidic protein （GFAP） and tyrosine hydroxylase （TH） were processed for valuation of glial activation and dopaminergic neuronal survival in the substantia nigra. Results： Obvious activation of microglial and astrocytic cells appeared in the substantia nigra of Lac animal model. Lac insult induced increasing expression of ibal and GFAP proteins compared to control. The ibal level significantly increased at Lac3 W and retained at Lac5 W （ P 〈 0.05 ）, while GFAP level increased at Lacl W and retained at Lac3 W and Lac5 W （P 〈 0.05）. The TH-positive neurons in the substantia nigra were remarkably decreased along with glial activation in the Lacl W, Lac3 W and Lac5 W （P 〈0.01 ）. Minocycline showed inhibition effect on microglial and astrocytic activation, and also improved dopaminergic neuronal survival in the substantia nigra compared to Lac5 W group （ P 〈 0.05 ）. Conclusion： Administration of microglial inhibitor Minocyline might show certain neuroprotection on nigral dopaminergic neurons possibly by intervention of abet rant glial activation in the Lac rat model.

关 键 词：LACTACYSTIN MINOCYCLINE 多巴胺能神经元 胶质细胞活化 帕金森病动物模型 

分 类 号：R742.5[医药卫生—神经病学与精神病学]