MPTP诱导的小鼠PD模型中相关脑区小胶质细胞反应性差异研究  

The different reactions of microglia in related brain regions in mouse model of Parkinson's disease induced by MPTP

作　　者：张志军[1,2] 董玉林[1] 刘晓娟[3] 刘娟[1] 夏春林[2] 倪衡建[1] 

机构地区：[1]南通大学医学院人体解剖学教研室神经生物学研究所,江苏省神经再生重点实验室,南通226001 [2]苏州大学细胞神经生物学研究室暨衰老与神经疾病实验室,苏州215123 [3]南通大学医学院微生物学教研室,南通226001

出　　处：《神经解剖学杂志》2009年第3期323-329,共7页Chinese Journal of Neuroanatomy

基　　金：江苏省高校自然科学研究指导性计划(06KJD310148)资助项目

摘　　要：为了探讨Parkinson病(PD)小鼠相关脑区的小胶质细胞反应性是否存在差异,本研究采用MPTP诱导的小鼠PD模型,用GSA I-B4-HRP组织化学染色方法对黑质致密部(SNc)、尾壳核(CPu)、腹侧被盖区(VTA)和额叶联合皮层(FrA)四个部位中小胶质细胞的形态和数量进行了观察;同时用免疫荧光染色检测了SNc和VTA中TH阳性神经元的数量,用Western blot方法检测CPu和FrA内TH蛋白含量的变化情况。结果显示:SNc中TH阳性神经元的数量和CPu中TH蛋白的含量在MPTP腹腔注射后1 d即大幅度降低(降幅约为68%);在MPTP腹腔注射后3 d起SNc中TH阳性神经元的数量和CPu中TH蛋白的含量逐步增加;小胶质细胞在MPTP腹腔注射后1～3 d的反应明显,然后逐渐减弱。VTA中TH阳性神经元的数量和FrA中TH蛋白的含量在MPTP腹腔注射后降幅不明显(降幅约在15%),小胶质细胞在MPTP腹腔注射后1 d的反应较为明显,其它时段的变化不显著。本研究结果提示:PD模型小鼠SNc和CPu中的小胶质细胞反应明显强于VTA和FrA区,反应性小胶质细胞在SNc中的多巴胺(DA)能神经元损伤过程中扮演了重要角色。To study the different reaction of microglia in the related brain regions in mouse model of Parkinson＇s disease （ PD）, the mouse model of PD induced by MPTP was applied. The microglia in substantia nigra compact part （ SNc）, cauda/a putamen （ CPu）, ventral tegmental area （VTA） and frontal association cortex （FrA） were detected by histochemi staining with GSA I-B4-HRP. Dopaminergic neurons in the SNe and VTA were detected by immunofluoreseence staining for TH. The content of TH protein in CPu and FrA were detected by Western blot. The results showed that, one day after MPTP treatment, the number of TH immunoreactive neurons in SNc and the content of TH protein in CPu were markedly decreased （about 68% loss）. Three days after MFFP treatment, the number of TH immunoreactive neurons and the content of TH protein were increased gradually. The reactive microglia were increased obviously in SNc and CPu during 1 - 3 days after MPTP treatment, and then decreased gradually. After MPTP treatment, the loss of TH immunoreactive neurons in VTA and the content of TH protein in FrA was not remarkable （about 15% loss）. The reactive microglia were only observed at one day after MPTP treatment in VTA and FrA. The present results indicate that the reaction of microglia in SNc and CPu are more remarkable than that in the VTA and FrA after MVFP treatment, the reactive microglia play a very important role in the injury of dopaminergic neurons in SNc.

关 键 词：PARKINSON病 MPTP 多巴胺能神经元 小胶质细胞 小鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]