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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。
Objective To establish a preclinical mouse model of Parkinson’s disease and to understand the histopathological changes before PD, especially the changes in substantia nigra and striatum ultrastructure and the number of synapses in mice. Methods Sixty mice of C57Bl / 6j mice were randomly divided into 4 groups. The preclinical mouse model of Parkinson ’s disease was established by multiple chronic administration of MPTP (4mg / kg.d). The ultrastructural changes of the substantia nigra and striatum were observed by light microscopy and electron microscopy. The dopamine levels in the striatum of the model mice were determined by chromatographic analysis. The limb movement coordination was detected by pole test Behavioral change. Results The degeneration of substantia nigra neurons in rat brain and the number of synapses in striatum were decreased. The content of dopamine in striatum of mice in each administration group decreased to different extents. At the same time, the quantitative and qualitative observations of mice behavioral in each experimental group No significant behavioral changes occurred. Conclusion Chronic administration of low dose MPTP can establish a preclinical mouse model of Parkinson’s disease. The results of this model, such as ultrastructure, biochemistry and animal behavior, can be used as a reference index to study the early stage of Parkinson’s disease.