帕金森病临床前期小鼠模型的建立

目的建立帕金森病临床前期的小鼠动物模型,了解帕金森病发病前的组织病理学改变,特别是小鼠中脑黑质、纹状体的超微病理及突触数量的变化。方法60只C57Bl/6j小鼠,采用小剂量MPTP多次慢性给药方法(4mg/kg.d)建立帕金森病临床前期小鼠动物模型。通过光学显微镜及电子显微镜观察小鼠黑质及纹状体的超微病理变化;利用色谱分析测定模型小鼠纹状体的多巴胺含量;通过动物爬杆试验(pole test)检测小鼠肢体运动协调的行为学改变。结果鼠脑黑质部分神经细胞变性及纹状体内突触数量减少;各给药组小鼠纹状体内多巴胺的含量均有不同程度的下降,同时各实验组小鼠行为学的定量及定性观察均未出现明显的行为学改变。结论低剂量MPTP慢性给药方式可以建立帕金森病临床前期的小鼠动物模型。该模型的超微形态学、生物化学及动物的行为学等结果可以作为研究帕金森病发病早期的参考指标。

A kind of preclinic stage mice model of pakinson's disease

Objective Establishing a Parkinson's disease mice model and investigate preclinic stage pathological changes and synapse quantity of Parkinson's disease with electron microscope. Methods 60 C57/Bl6j mice injected 1-methyl-4-pheny-1. 2. 3.6-tetrahydropydine (MPTP) to set up a chronic model of Parkinson's disease. The present study observed the neuron degeneration in substantia nigra and decrease of the synapse number in striatum in the chronic MPTP-treated mice model. Dopamine of the striatum was measured by HPLC-ECD. Results The present study synapse number in striatum in the chronic MPTP-treated mice model. There was a significant difference (P < 0.01) on content of DA in the striatum between the control and MPTP-treated groups. Conclusion The investigation indicate that the low dose MPTP can set up a preclinic stage Parkinson's disease animal model. There was a significant difference (P < 0.01) on content of DA in the striatum between the control and MPTP-treated group. These changes of ultramorphological, biochemical and behavioral of the model mice may be make a reference index of Parkinsons's disease early stage.