MPTP诱导猴帕金森病模型全脑糖代谢变化研究
Changes of Glucose in the Brains of Monkeys with MPTP Induced Parkins on’s Disease
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摘要: 目的 探索帕金森病猴行为学和脑葡萄糖代谢变化特点,进一步了解帕金森病病理生理机制。 方法 选取健康成年猕猴4只,经适应性饲养后采用以18F标记的脱氧葡萄糖(DG)为示踪剂的正电子发射计算机断层扫描(18F DG-PET-CT)进行全脑糖代谢检测。采用经外周静脉连续注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)溶液,建立全身性猴帕金森病模型。对模型猴进行行为学评分。建模成功3个月后,再次对模型猴进行脑18FDG-PET-CT扫描。对比分析建模前后模型猴脑葡萄糖代谢变化,并行脑组织病理检测。 结果 4只猕猴均建模成功。模型猴表现出典型的运动迟缓、肌僵直、运动减少等帕金森病样症状,行为学评分均超过20分,经左旋多巴治疗后,帕金森病样症状显著缓解。模型猴还表现出淡漠、攻击性减退等高级神经活动改变。18FDG-PET-CT显示,帕金森病模型猴脑葡萄糖代谢显著降低,且并不局限于黑质纹状体区域。 结论 本研究发现帕金森病猴神经代谢变化范围广泛,这可能是导致帕金森病非运动症状的重要因素。Abstract: Objecitve To examine the metabolic and behavioral changes of monkeys with MPTP induced Parkinson's disease. Methods Four healthy monkeys were injected with diluted MPTP solution continuously through peripheral veins. The behavioral changes of the monkeys were monitored with the Parkinson disease scale for monkeys.18FDG-PET-CT scans for the whole brain were obtained before and 3 months after the injection of MPTP. The pathological and glucose metabolic changes of the brains were examined. Results The animal model of Parkinson's disease was successfully established in all 4 monkeys, showing typical parkinsonian syndromes of bradykinesia, rigidity and hypokinesia. Changes in high nervous activities such as apathetic and less aggressive behaviors were also observed. Their scores of Parkinson disease scale exceeded 20. The parkinsonian syndromes were relieved after the administration of sinemet. The 18FDG-PET-CT scans showed significant glucose reduction after the MPTP injection within and outside of the basal ganglion area. Conclusion The metabolic changes of brains in the monkeys with Parkinson's disease are not limited to the basal ganglion area, which may be an important mechanism for the non-motor symptoms.