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帕金森病大鼠模型黑质白介素-6表达的实验研究
The role of microglia and interleukin in the pathogenesis of Parkinson’s disease
【摘要】 目的探讨白介素-6(IL-6)和小胶质细胞在帕金森病发病机制中作用,阐述小胶质细胞激活后作用的合理模式。方法采用立体定向术将神经毒素6-羟基多巴(6-OHDA)注入大鼠右侧纹状体制作偏侧帕金森病大鼠模型。造模2月后,计数黑质致密部神经元和小胶质细胞数目,观察黑质致密部病理形态学变化,并采用免疫组织化学方法观察黑质致密部IL-6表达水平的变化。结果光镜下观察模型组右侧黑质致密部多巴胺能神经元几乎消失,小胶质细胞数目明显增多,与假手术组及正常对照组相比,差异有显著性(P<0.05)。免疫组化染色显示模型组右侧黑质致密部可见明显的小胶质细胞核周的棕褐色阳性表达,而模型组左侧与假手术组及正常对照组右侧黑质均未见明显阳性着染区。结论神经毒素6-OHDA可导致神经元释放小胶质细胞激活态物质,激活小胶质细胞释放IL-6介导细胞毒作用,促进神经元的慢性变性坏死。
【Abstract】 Objective To explore the role of IL-6 and microglia in the pathogenesis of Parkinson’s disease (PD),and establish a consistent pattern implicating microglia as the effector for the pathogenesis of PD.Methods The 6-OHDA was stereotaxically injected into the right striatum of rats at two sites to fabricate unilateral rats PD model.After two months,we counted the alternation in quantity of microglia and the dopaminegic neurons,ob- served the deletion of the dopaminegic neurons and proliferation of the activated microglia,and observed the expres- sion of IL-6 in the substantia nigra compacta by immunohistoehemical stain under optical microscope.Results The quantity of the dopaminegic neurons in the right substantia nigra compacta of PD model group was obviously deleted,however the microglia was obviously increased.Compared with the sham group and control group,there were significant difference(P<0.05).Immunohistochemical stain showed that IL-6 were positively expressed with brown color round the nucleus of microglia.While there was no positive expression in the left substantia nigra compacta in PD model group and the sham-operation group,normal control group.Conclusion When the 6-OH- DA was retrograde absorbed by the neurons,neurons release substances that influence the state of activation of mi- croglia.The activated microglia released immune cytokines IL-6 induced eytotoxic lysis,then cause the neurons chronic degeneracy and necrosis.
【Key words】 6-hydroxydopamine; Parkinson disease/etiology; Substantia nigra; Microglia; Interleukin-6;
- 【文献出处】 中风与神经疾病杂志 ,Journal of Apoplexy and Nervous Diseases , 编辑部邮箱 ,2007年05期
- 【分类号】R742.5
- 【被引频次】2
- 【下载频次】190