垂体同源盒家族因子3和孤儿核受体相关因子1基因在帕金森病模型大鼠腹侧中脑表达显著下调

Remarkable decline of Pitx3 and Nurr1 genes expressions in the ventral mesencephalon in the model rats with Parkinson's disease

目的:探讨垂体同源盒家族因子3(Pitx3)和孤儿核受体相关因子1(Nurr1)基因在帕金森病(PD)模型大鼠腹侧中脑的表达变化。方法:(1)采用免疫荧光方法检测PD模型组、成年正常组和假手术组大鼠腹侧中脑TH、Pitx3/TH和Nurr1/TH阳性细胞并计数;(2)分别采用半定量RT-PCR和Western Blot方法检测Pitx3和Nurr1基因在PD模型组、成年正常组和假手术组大鼠腹侧中脑转录和翻译水平的变化。结果:(1)免疫荧光检测显示PD大鼠模型组腹侧中脑多巴胺能神经元数目显著减少;(2)半定量RT-PCR和Western Blot检测显示PD大鼠模型组腹侧中脑左侧Pitx3和Nurr1表达显著下调,其中Pitx3表达下调更明显。结论:Pitx3和Nurr1基因的持续表达与腹侧中脑多巴胺能神经元的生存维持密切相关,为探索PD的病因诊断及基因治疗提供可能的新途径。

Objective： To explore the variation of Pitx3 and Nurr1 genes expressions in the ventral mesencephalon in the model rats with Parkinson＇s disease（ PD）. Methods：（1） Immunofluorescence was used to observe and count the number of tyrosine hydroxylase（ TH）,Pitx3 / TH and Nurr1 / TH positive cells in the ventral mesencephalon in healthy group,sham-operated group and PD model group.（2） Both m RNA and protein expressions of Pitx3 and Nurr1 gene were measured respectively using semiquantitative RT-PCR and Western Blot in each group. Results：（ 1） Immunofluorescence staining showed a significant decline of the numbers of dopaminergic neurons in the ventral mesencephalon of model rats with PD.（2） RT-PCR and Western blot assay showed that the levels of Pitx3 and Nurr1 of the left side of ventral mesencephalon in model rats group with PD were lower than the two other groups. The expression of Pitx3 decreased more obviously. Conclusion： The continuing expression of Pitx3 and Nurr1 genes was probably related with the survival of the dopaminergic neurons in the ventral mesencephalon. It might be a potential target for the etiological diagnosis and a novel therapeutic target for PD.