MPTP诱导慢性帕金森病小鼠模型的实验研究

The establishment of chronic parkinson’s desease in mouse model induded by mptp

目的:观察慢性长期小剂量注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)对小鼠黑质多巴胺能神经元损伤及α-突触核蛋白(α-synuclein蛋白)表达的影响。方法:C57BL小鼠背部皮下注射MPTP 25mg/kg体重,每周注射2次,连续注射5周,观察小鼠行为学改变,应用免疫组化染色检测酪氨酸羟化酶(Throsine hydroxylase,TH)和α-突触核蛋白(α-synuclein,α-syn)的表达,原位末端标记法(TUNEL法)检测多巴胺能神经细胞凋亡。结果:与注射生理盐水组相比,注射MPTP组小鼠出现短暂一过性的震颤、后腿拉直、躬背、竖毛、运动减少等;黑质部酪氨酸羟化酶阳性细胞数目减少,α-突触核蛋白阳性细胞数目增加;生理盐水组未观察到细胞凋亡,MPTP组存在凋亡现象。结论:慢性长期注射MPTP可诱导小鼠行为学改变,黑质部多巴胺神经元细胞凋亡,以及α-突触核蛋白持续表达增多和聚集。

Objective：To investigate dopaminergic neuron injury and α-synuclein expression of mouse exposed chronically to low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）. Methods：The C57BLmice received bake hypodermic injections of 25 mg/kg MPTP twice a week for 5 consecutive weeks. Abnormal behavior was observed during the treatment by using herbicide. The expression of throsine hydroxylase（TH）and α-synuclein was determined by immunohistochemistry. The dopaminergic neurons apoptosis was determined by TdT-mediatd dUTP-biotin nick end labeling （TUNEL）. Results：As compared with the controls of mice,those treated with MPTP displayed markedly hypoactive behavior. Immunohistochemical staining showed that the numbers of TH stain cells was decreased significantly after treatment with MPTP,and the density of α-synuclein stain was increased significantly after treatment with MPTP. Apoptosis displayed after treatment with MPTP. Conclusion：Chronical injection with MPTP might induce abnormal behavior. apoptosis and continual aggregation of α-synuclein in dopaminergic neurons of substantial nigra.