偏侧帕金森病猴模型的评价

Evaluation on the Hemiparkinsonism Monkey Model

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 The 1 - methyl - 4 -phenyl - 1,2,3,6 -tetrahydropyridine (MPTP)induced hemiparkinsonian monkey model was evaluated from the parameters of animalbehavior, function of dopamine transporter, dopamine and dopaminergic neurons.Methods Monkey models with hemiparkinsonism were induced by the unilteral infusion ofMPTP into the right common carotid artery. The activity of striatal dopamine transporterwas detected by single photo emission computed tomography (SPECT) with 99mTc-TRODA- T-1. The extracellular dopamine and its metabolites of the striatum were measured bymicrodialysis combined with high performance liquid chromatography and electrochemicaldetection(HPLC-ECD). Neuropathological changes were examined by immunohistochemicalassay. Results The activity of dopamine transporter in the striatum was decreased in theMPTP - treated side compared with the untreated side. the levels of extracellular dopamine,DOPAC and HVA in the striatum of the MPTP - treated side were reduced by 70%, 34% and38% respectively, as compared with those of the untreated side. There was a marked loss oftyrosine hydroxylase - positive cells and fibers in the substantia nigra and striatum of theMPTP - treated side. Conclusion The hemiparkinsonian monkey model induced by MPTPmay resemble the early stage of Parkinson's disease. The in vivo determination ofdopamine transporter and dopamine by SPECT and microdialysis is a good approach to thestudy of Parkinson's disease.