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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,并探讨该变化与黒质酪氨酸羟化酶(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-1,1 h后取左右纹状体,以γ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大鼠黒质组织进行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,99mTc-PRODAT-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 the dynamic changes of dopamine transporter (DAT) in the striatum of Parkinson’s disease (PD) rats with different course of disease and to explore the relationship between the changes and the content of tyrosine hydroxylase (TH). Methods: A bilateral PD model was established by injecting 6-OHDA into the right substantia nigra pars compacta and medial forebrain in rats. At 2 weeks, 4 weeks and 6 weeks after modeling, 99mTc-TRODAT-1 was injected into the caudal vein of rats and the left and right striatum were taken from the caudal vein. The radioactivity count was measured by gamma counter. The left and right of unit mass Radioactive count rate and left and right striatal mass radioactivity count ratio. At the same time, TH immunostaining was performed on the substantia nigra of PD rats at 2, 4 and 6 weeks after modeling to observe the morphology and distribution of positive cells. Results: The radiation counts of damaged striatum in PD rats were significantly lower than those in healthy side. The relative radioactivity of DAT in PD rats decreased by 16.8%, 35.9% and 50.1% respectively at 2, 4 and 6 weeks after modeling (P <0.05-0.001). There was a positive correlation between the relative radioactivity of DAT and the number of TH-positive cells in the lesioned side of PD rats (P <0.01, R = 0.9, n = 15). CONCLUSION: DAT levels in striatum of PD rats decrease gradually with the course of disease increasing. The radioactive distribution of 99mTc-PRODAT-1 can reflect the changes of presynaptic dopaminergic neurons more accurately.