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单侧脑室和双侧脑室定位注射MPP⁺制作帕金森病猴模型的比较研究

李俊^1,2, 张会云^1,2, 江勇³, 李天晴^1,2,*

¹昆明理工大学灵长类转化医学研究院，昆明 650000；²云南中科灵长类生物医学重点实验室，昆明 650500；³云南省第一人民医院核医学科，昆明 650032

摘要

帕金森病(Parkinson’s disease, PD)是最常见的中枢神经系统退行性疾病之一，但目前其发病机制仍不明了。现阶段已成功建立了通过单侧脑室给予1-甲基-4-苯基吡啶离子(MPP⁺)的PD造模方法，但该方法存在多种问题，不能很好地模拟PD发病机制。本研究旨在对单侧脑室给药方法进行改进，通过双侧脑室注射低剂量MPP⁺建立慢性PD猴模型，并在造模时间、模型稳定性、模型表征以及99Tcm-TRODAT-1单光子发射计算机断层成像术(single-photon emission computed tomography, SPECT)脑显像数据方面进行两种造模方法的对比分析。结果显示，相对单侧造模组，双侧造模组的恒河猴PD症状出现得更快、更明显，给药结束后症状维持时间更长；单侧造模组猴左右两侧纹状体损毁不对称，左侧(给药侧)纹状体放射性摄取明显减弱，对侧受损较轻，而双侧造模组猴两侧纹状体放射性分布均显著缺失，呈明显的对称损毁。以上结果提示，双侧脑室给药造模方法的效果明显优于单侧脑室给药，可以为PD相关研究提供更加理想的动物模型。

关键词： 帕金森病; 非人灵长类动物模型 ; 侧脑室双侧定点注射 ; 侧脑室单侧定点注射

分类号：Q95-33;R742.5

Comparison of Parkinson’s monkey models induced by unilateral and bilateral intracerebroventricular injections of MPP⁺

LI Jun^1,2, ZHANG Hui-Yun^1,2, JIANG Yong³, LI Tian-Qing^1,2,*

¹Institute of Translational Medicine, Kunming University of Science and Technology, Kunming 650000, China；²Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China；³Department of Nuclear Medicine, the First People’s Hospital of Yunnan Province, Kunming 650032, China

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases, but its pathogenesis is still unclear. Recently a new approach has been used to develop Parkinsonian monkeys with unilateral intracerebroventricular injections of 1-methyl- 4-phenylpyridinium ion (MPP⁺). However, this new method still has some shortcomings, which limits the potential application of MPTP-induced PD monkey models. In the present study, we aimed to develop a modified protocol to induce chronic Parkinsonian non-human primate model with low-dose MPP⁺ by bilateral intracerebroventricular injections. The induced time of PD model, model stability, phenotypes and 99Tcm-TRODAT-1 single-photon emission computed tomography (SPECT) brain imaging of dopamine transporter were compared between unilateral and bilateral modeling groups. The results showed that PD symptoms in the bilateral modeling group were induced earlier, more serious, and lasted longer after the administration stage, compared with those of the unilateral modeling group. In the unilateral modeling group, radioactive uptake of the striatum was decreased significantly in the left side (MPP+ injected side), but unaffected in the right side. While in the bilateral modeling group, the radioactive uptake of the bilateral striatum was declined dramatically and symmetrically. These results suggest that bilateral intracerebroventricular injection of MPP⁺ is superior to unilateral intracerebroventricular injection in establishing chronic Parkinsonian non-human primate model and may supply a better animal model for PD research.

Key words: Parkinson’s disease; non-human primate animal model ; bilateral intracerebroventricular administration ; unilateral intracerebroventricular administration

收稿日期：2017-01-31　　录用日期：2017-11-06

通讯作者：李天晴　　E-mail: litq@lpbr.cn

DOI: 10.13294/j.aps.2017.0084

引用本文：

李俊, 张会云, 江勇, 李天晴. 单侧脑室和双侧脑室定位注射MPP⁺制作帕金森病猴模型的比较研究[J]. 生理学报 2017; 69 (6): 743-750.

LI Jun, ZHANG Hui-Yun, JIANG Yong, LI Tian-Qing. Comparison of Parkinson’s monkey models induced by unilateral and bilateral intracerebroventricular injections of MPP⁺ . Acta Physiol Sin 2017; 69 (6): 743-750 (in Chinese with English abstract).