不同病程帕金森病大鼠纹状体多巴胺转运蛋白的动态变化

The dynamic changes of striatal dopamine transporter in the progression of Parkinson's disease in rats

目的：观察不同病程帕金森病（PD）大鼠纹状体多巴胺转运蛋白（DAT）的动态变化，并探讨该变化与黑质酪氨酸羟化酶（TH）之间的关系。方法：采用双点注射6-OHDA至大鼠右侧黑质致密部和前脑内侧束，建立偏侧PD模型。建模后2周、4周、6周的PD大鼠分别尾静脉注射99mTc-TRODAT-1，1h后取左右纹状体，以1计数仪测定放射性计数，并计算单位质量的左、右放射性计数率以及左、右纹状体单位质量的放射性计数比值。同时取建模后2周、4周、6周PD大鼠黑质组织进行TH免疫染色，观察阳性细胞形态及分布。结果：PD大鼠毁损侧纹状体放射计数明显低于健侧，建模后2周、4周、6周PD大鼠DAT相对放射计数较健侧分别降低了16．8％、35．9％和50．1％（P〈0．05～0．001）；不同病程PD大鼠毁损侧纹状体DAT的相对放射计数与TH阳性细胞数呈高度的正相关（P〈0．01，R=0．9，n=15）。结论：PD大鼠纹状体DAT含量随着病程的增加逐渐减少，“Tc—PRO-DAT-1的放射性分布能够较准确的反映突触前多巴胺能神经元的变化。

Objective： To observe dynamic changes in striatal dopamine transporter （DAT） in progression of Parkinson ＇s disease （PD）, and to investigate the relationships between changes of DAT and tyrosine hydroxylase （TH） expression in substantia nigra. Methods： A hemiparkinsonium rat model was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta （SNc） and the right medial forebrain bundle （MFB）. Rats were injected with ~mTc-TRODAT-1 through tail vein at 2, 4 and 6 weeks post-lesion, respectively. Both the left and right striata were re- moved after 1 h, the densities of DAT were measured using ~/radioactive counting meter, then the radioactive counts rate per unit mass of striatum on both sides and radioactivity of the striatum count ratio radioactive count on the right to that on the left sidie were calculated. Meanwhile, the morphology and distribution of TH immunoreactive positive cells in the sub- stantia nigra （SN） were observed at 2, 4 and 6 weeks post-lesion. Results： The radioactive counts on the lesioned side of SN in PD rats was significantly lower than that of unlesioned side, and it was decreased by 16.8% ,35.9% and 50.1% respectively when compared with the unlesioned side at 2, 4, and 6 weeks （P 〈 0.05 - O. 001, n = 5）. There was a sig- nificant positive correlation between radioactive counts and TH immunoreactive positive cells in PD rats at 2, 4, and 6 weeks （P 〈0.01 ,R =0.9,n = 15）. Conclusion： The density of DAT decreased gradually with the PD progression, and 99mTc-PRODAT-1 distribution of radioactivity may reflect the changes in presynaptic dopaminergic neurons.