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目的:探讨百草枯对黑质部多巴胺能神经元的损害是否具有选择性。方法:用口服百草枯的途径,建立小鼠帕金森病模型;应用原位杂交技术观察DAT和VMAT2在不同脑区的mRNA表达水平并测定两者的比值,采用细胞计数观察百草枯干预后多巴胺能神经元的损害。结果:在黑质部DATmRNA和VMAT2mRNA的比值最高;在红核和下丘脑室旁核区域DATmRNA与VMAT2mRNA的比值和黑质部相比较低(P<0·01)。百草枯干预后黑质部的多巴胺能神经元减少37·7%;红核和下丘脑室旁核区的多巴胺能神经元分别减少12·2%和13·1%。结论:百草枯对黑质部多巴胺能神经元的损害具有相对选择性,其原因可能与黑质部DATmRNA和VMAT2mRNA的比值高有关。
Objective: To investigate whether paraquat is selective for the damage of substantia nigra dopaminergic neurons. Methods: The mouse model of Parkinson’s disease was established by oral administration of paraquat. The mRNA expression levels of DAT and VMAT2 in different brain regions were observed by in situ hybridization and the ratio of the two was determined. The cell count was used to observe the dopaminergic Neuronal damage. Results: The ratio of DAT mRNA to VMAT2 mRNA in substantia nigra was the highest. The ratios of DAT mRNA to VMAT2 mRNA in nucleus accumbens and hypothalamic paraventricular nucleus were lower than those in substantia nigra (P <0.01). After paraquat intervention, dopaminergic neurons decreased by 37.7% in substantia nigra and decreased by 12.2% and 13.1% in nucleus pulposus and paraventricular nucleus of hypothalamus respectively. CONCLUSION: Paraquat is relatively selective for the damage of substantia nigra dopaminergic neurons, which may be related to the high ratio of DAT mRNA and VMAT2 mRNA in substantia nigra.