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目的通过测定行为、纹状体多巴胺转蛋白、多巴胺及黑质纹状体多巴胺能神经元评价应用ＭＰＴＰ制备的偏侧帕金森病猴模型。方法经右侧颈总动脉注射ＭＰＴＰ制备偏侧帕金森病猴模型，应用９９ｍＴｃ－ＴＲＯＤＡＴ－１ＳＰＥＣＴ显像观察纹状体多巴胺转运蛋白功能；采用微透析结合高效液相一电化学法检测纹状体细胞外液多巴胺（ＤＡ）及其代谢产物（ＤＯＰＡＣ、ＨＶＡ）含量；免疫组化法观察黑质纹状体酪氨酸羟化酶（ＴＨ）阳性神经元及纤维。结果ＭＰＴＰ注射侧多巴胺转运蛋白密度低于未注射侧，左右侧纹状体感兴趣区的比值为１．１０～１．１８。与未注射侧相比，ＭＰＴＰ注射侧纹状体细胞外液ＤＡ、ＤＯＰＡＣ、ＨＶＡ分别降低７０％、３４％和３８％，黑质和纹状体ＴＨ阳性细胞及纤维为对侧的１０％～１５％。结论应用ＭＰＴＰ制备的偏侧帕金森病猴模型与人类早期帕金森病有一定的相似性。微透析和ＳＰＥＣＴ在体检测多巴胺转运蛋白和多巴胺是研究帕金森病的有效手段。
OBJECTIVE: To assess the behavioral, dopaminergic, dopamine and nigrostriatal dopaminergic neurons in striatum for the evaluation of a hemiparkinsonian monkey model using MPTP. Methods The model of hemiparkinsonism was made by injection of MPTP on the right common carotid artery. The striatal dopamine transporter function was observed by 99mTc-TRODAT-1 SPECT imaging. The striatum was detected by microdialysis combined with high performance liquid phase-electrochemical Extracellular dopamine (DA) and its metabolites (DOPAC, HVA) were detected by immunohistochemical method. Tyrosine hydroxylase (TH) positive neurons and fibers of nigrostriatal tissue were observed by immunohistochemistry. Results The density of dopamine transporter (MPTP) on the injection side of MPTP was lower than that on the non-injection side, and the ratio of the regions of interest in the left and right striatum was 1.10-1.18. Compared with the uninjected side, the extracellular DA, DOPAC and HVA in the striatum of the MPTP injection were reduced by 70%, 34% and 38%, respectively. The numbers of TH positive cells and fibers in the substantia nigra and striatum were 10% 15%. Conclusion The hemiparkinsonism monkey model developed by MPTP has some similarities with human early-stage Parkinson’s disease. Microdialysis and SPECT in vivo detection of dopamine transporter and dopamine is an effective means of studying Parkinson’s disease.