MPTP诱导的食蟹猴偏侧帕金森病模型运动行为学的长期动态评价研究

目的 建立具有长期运动行为学改变的灵长类动物模型，用于研究神经保护性药物的研究。利用不同运动变化评估方法探讨1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）诱导的食蟹猴偏侧帕金森病（Parkinson's disease，PD）模型运动行为学的长期动态变化。方法 5只（6~7岁）健康雄性食蟹猴分别于左侧颈内动脉注射MPTP建立偏侧PD模型。在MPTP注射前（基线），注射后3、6个月及1、3、6年分别进行临床评分；在MPTP注射前，注射后3、6个月及1年和6年分别进行24 h躯体自发运动总量行为监测。结果 造模后3个月临床评分（14.65±8.41）增高到达高峰，造模6个月后临床评分（8.10±2.01）仍较基线高，但与3个月时比较显著降低（P=0.006）；之后维持稳定，直至造模6年后临床评分与6个月时比较差异无统计学意义。而24 h躯体自发运动总量造模后3个月降低最明显（16 597.79±12 488.87），造模后6个月有所恢复（29 278.02±12 264.66），但与基线（50 084.20±30 170.89）比较仍显著性降低（与3、6个月比，P值分别为0.014，0.016）；造模1年和6年后的24 h躯体自发运动总量恢复到基线水平。结论 颈内动脉注射MPTP可以诱导形成稳定具有长期运动症状的偏侧PD模型，尤其是临床评分的改变，直到造模后6年仍存在异常。

Long lasting changes of motor function in MPTP-induced unilateral cynomolgus monkeys model

Objective To establish long lasting changes of motor function in MPTP-induced non-human primate models for investigating neuroprotective therapy. We try to study the dynamic changes of motor function of MPTP-induced unilateral Parkinson's disease model in cynomolgus monkeys. Methods Total 5 healthy male cynomolgus monkeys (6~7 years old) were injected MPTP into the left internal carotid artery. The motor behavior changes were evaluated by clinical rating score and physical activity monitoring before and after MPTP injection at 3 and 6 months, 1, 3, and 6 years. Results The clinical rating score was significantly increased and reached the peak (14.65±8.41) at 3 months and partially recovered at 6 months (8.10±2.01, P=0.006), but maintained stable to 6 years after MPTP injection. The 24 h physical activity was significantly decreased and reached the peak at 3 months (16 597.79±12 488.87, P=0.014), 6 months (29 278.02±12 264.66, P=0.016) but recovered to the baseline level (50 084.20±30 170.89) after 1 year. Conclusion The results suggest that the motor deficit assessed by clinical rating score of MPTP-induced unilateral Parkinson's disease model in cynomolgus monkeys can last up to 6 years.