99mTc-TRODAT-1放射自显影对帕金森病大鼠模型多巴胺转运蛋白的观察

目的　探讨 99m Tc- TRODAT- 1多巴胺转运蛋白 (DAT)显像临床应用价值。　方法　应用 6 -羟基多巴胺 (6 - OHDA)建立完全损毁及部分损毁一侧帕金森病 (PD)大鼠模型 ,以 99m Tc-TRODAT- 1作为配体 ,采用放射自显影观察一侧 PD大鼠模型 DAT分布及其密度 ,高效液相 -电化学方法检测模型大鼠纹状体多巴胺 (DA)及其代谢产物含量 ,免疫组化酪氨酸羟化酶 (TH)染色观察模型大鼠黑质及纹状体 TH阳性细胞及纤维。　结果　 6 - OHDA损毁侧纹状体放射性浓集明显低于未损毁侧 ,完全损毁模型的纹状体放射性浓集最低。纹状体 DA含量部分损毁及完全损毁较未损毁侧分别降低 39%和 98%。TH染色可见损毁侧黑质及纹状体 TH阳性细胞及纤维明显少于对侧。　结论　 PD大鼠模型损毁侧纹状体 DAT密度降低 ,且与损毁程度有关。99m Tc- TRODAT- 1DAT显像研究可能有助于 PD的早期诊断。

Autoradiographic study on dopamine transporter in rat model of Parkinson's disease with ~(99m)Tc-TRODAT-1

Objective To evaluate the clinical effect of dopamine transporter(DAT) imaging with 99m Tc TRODAT 1 . Methods Completely and partially lesioned rat models of hemiparkinsonism were rendered by an unilateral infusion of 6 hydroxydopamine (6 OHDA) into the right substantia nigra and median forebrain bundle or substantia nigra alone. Distribution and density of DAT in rat models of hemiparkinsonism were evaluated by autoradiography with 99m Tc TRODAT 1. The levels of dopamine(DA) and its metabolites were measured with high performance liquid chromatography and electrochemical detection(HPLC ECD). The tyrosine hydroxylase(TH) positive cells and fibres in substantia nigra and striatum of the models were observed with immuno histochemical staining. Results The radioactivity in the lesioned striatum was significantly decreased as compared with that in the intact one. The radioactivity in the lesioned striatum of the completely lesioned model was lower than that of the partially lesioned model. The levels of DA in the lesioned striatum of the partially and completely lesioned models decreased by 39% and 98%, respectively, as compared with those of the unlesioned one. The loss of TH positive cells and fibres in the substantia nigra and striatum was found in the lesioned side of both the completely and partially lesioned models. Conclusions The density of DAT in the lesioned striatum is markedly reduced in the hemiparkinsonian rat models, and it is related with the degree severity of the lesion. Imaging study of DAT may be helpful for the early diagnosis of Parkinson's disease.