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  

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

作　　者：罗斌斌 胡亚松 岳峰 陈彪[1,2] Luo Binbin;Hu Yasong;Yue Feng;Chen Biao(Key Laboratory of Longevity and Ageing-Related Diseases,Ministry of Education,Center for Translational Medicine,Basic Medical College,Guangxi Medical University, Nanning 530000,China;Department of Neurobiology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]广西医科大学基础医学院转化医学研究中心,长寿与老年相关疾病教育部重点实验室,南宁530000 [2]首都医科大学宣武医院神经生物学研究室,北京100053

出　　处：《首都医科大学学报》2018年第2期217-222,共6页Journal of Capital Medical University

基　　金：国家科技支撑计划(2007BAI33B01),国家自然科学基金(31472056),广西科技基础条件平台建设项目(20164412-3),南宁市科学研究与技术开发计划项目(20163349)。

摘　　要：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。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.

关 键 词：帕金森病 食蟹猴 运动行为学 1-甲基-4-苯基-1 2 3 6-四氢吡啶 

分 类 号：R742.5[医药卫生—神经病学与精神病学]