百草枯诱导小鼠α-突触核蛋白表达升高并聚集的实验研究  

Paraquat Causes Up-regulation and Aggregation of α-synuclein in Mice

作　　者：杜芸兰[1] 刘振国[1] 陈生弟[1] 陆国强[1] 胡庆沈[2] 

机构地区：[1]上海第二医科大学附属瑞金医院神经内科,帕金森病诊疗与研究中心,上海200025 [2]上海第二医科大学细胞生物学实验室,上海200025

出　　处：《中国神经免疫学和神经病学杂志》2005年第1期14-17,33,i001,共6页Chinese Journal of Neuroimmunology and Neurology

基　　金：上海市科委青年科技"启明星后"计划基金资助项目(97QMB1410);上海市教委发展基金资助项目(03BK24)

摘　　要：目的　观察除草剂百草枯诱导小鼠黑质细胞α 突触核蛋白(α- synuclein,α- Syn)表达及聚集,探讨环境因素在帕金森病(Parkinson disease,PD)发病中的作用机制。方法　C57BL小鼠按体重 10 mg/kg经腹腔注射百草枯,应用原位杂交、RT PCR分析α- Syn mRNA表达,免疫组化、免疫荧光双标染色观察黑质区α- Syn 显色,并进一步确定表达α- Syn的神经元表型及α Syn聚集。结果　注射百草枯组小鼠黑质区α-Syn mRNA表达量升高,α- Syn阳性细胞数相对增加;α- Syn与硫磺素、酪氨酸羟化酶(tyroxine hydroxylase,TH)及硫磺素复合染色的阳性细胞数均升高。结论　百草枯诱导小鼠黑质细胞α- Syn表达升高并出现蛋白聚集可能是导致PD发病的机制之一。Objective To investigate α-synuclein(α-Syn) expression and aggregation in dopaminergic neurons of mouse substantia nigra exposed to paraquat, and the role of the relationship of α-Syn and paraquat in the pathogenesis of Parkinson disease. Methods The C57BL mice received intraperitoneal injections of 10 mg/kg paraquat. The level of mRNA ofα-synuclein was determined with in situ hybridization and RT-PCR. The phenotype of neurons, and expression and aggregation of α-Syn was detected by immunohistochemistry and double labeling immunofluoresence stain. Results The immunohistochemical staining showed that the number of α-synuclein positive neurons was relatively increased and the level of mRNA of α-Syn was high indeed after treated with paraquat. The numbers of colocalization positive neurons with thioflavine S and α-Syn, as well as thioflavine S and TH, were also increased,were observed in the confocal imaging of double labeling immunofluroscene. Conclusions Paraquat can induce up-regulation and aggregationofα-Syn in the dopaminergic neurons of substantia nigra, and it is one of pathways of paraquat inducing parkinsonism.

关 键 词：百草枯 帕金森病 Α-突触核蛋白 聚集 

分 类 号：Q786[生物学—分子生物学]