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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。
Parkinson’s disease (PD) is one of the most common central nervous system degenerative diseases, but its pathogenesis is still unclear. At this stage, we have successfully established a PD modeling method that uses 1-methyl-4-phenylpyridinium ion (MPP +) in unilateral ventricle. However, this method has many problems and can not well model the pathogenesis of PD. The purpose of this study was to improve the unilateral intraventricular administration by establishing a chronic PD monkey model by low-dose MPP + injected into the bilateral ventricle. The model was established by modeling time, model stability, model characterization and 99Tcm-TRODAT-1 single photon emission computer Comparison of two modeling methods in single-photon emission computed tomography (SPECT) brain imaging data. The results showed that, compared with unilateral model group, bilateral rhesus PD model group appeared faster, more obvious symptoms, after the end of the symptoms to maintain longer; monotypic monkey left and right sides of the pattern Body damage asymmetry, the left (administration side) striatum radioactive uptake was significantly weakened contralateral damage less, while the two sides of the model group on both sides of the monkey striatum radioactive distribution were significantly missing, showing a significant symmetry damage . These results suggest that the double intraventricular injection modeling method is better than single intraventricular administration, can provide a more ideal animal model for PD related research.