皮下注射MPTP诱导猕猴双侧慢性帕金森病模型的制作  

Establishment of model of bilateral chronic Parkinson disease by subcutaneous injection of MPTP in Rhesus Macaques(Macaca mulattas)

作　　者：朱岳峰[1] 董乐[1] 樊晶鑫 杨正明[1] 雷霆[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经外科,武汉430030

出　　处：《中国临床神经外科杂志》2014年第12期735-737,共3页Chinese Journal of Clinical Neurosurgery

基　　金："国家临床重点专科"项目资助(2012303);武汉市科学技术计划项目(201060938360-06)

摘　　要：目的探讨猕猴双侧慢性不可逆性帕金森病（PD）模型的制作方法。方法 4只猕猴分别采用不同剂量（0.1 mg/kg/d和0.4 mg/kg/d）和不同频率（每天一次和隔天一次）及不同次数皮下注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）制作PD模型,注射MPTP前后观察行为学表现并进行非人类灵长类PD评分量表（PPRS）评分。结果猕猴注射MPTP一段时间后开始出现PD症状,主要表现为倦怠、迟缓;继续给药PD症状会出现进行性快速加重导致后续动物因进食困难而死亡;若过早停止给药,则导致PD模型不稳定,动物症状可自愈。采用剂量为0.1 mg/kg/d的MPTP连续皮下注射14 d后,猕猴出现中度PD症状（PPRS评分为6~8分）时,改隔日注射一次,共4次,猕猴出现不可逆性PD症状,且可自主摄食并长期存活,是一个成功的模型。结论适量皮下注射MPTP可制作猕猴慢性、不可逆性、双侧PD模型,其更接近人PD的临床特征,且无需鼻饲喂养可长期存活。Objective To explore the optimal method to estabish bilateral chronic irreversible Parkinson disease model in monkey Method Four Rhesus Macaques were used in the study. The subcutaneous injections of 0.1 mg/kg body weight 1-methyl-4-pbenyl-l, 2, 3, 6-tetrahydrepyridine （MPTP） were performed once a day in 3 monkeys for 14, 14 and 19 days respectively. The subcutaneous injections of 0.4 mg/kg body weight MPTP were performed once a day in a monkey for 7 days. The behavior was observed before and after the injection of MPTP in all the animals. Results ① One animal, who presented significant symptoms of Parkinson disease and dysphagia after continuous subcutaneous injection of MPTP （0.4 mg/kg/d） for 7 days, died 16 days after the injection. ② One animal, who presented significant symptoms of Parkinson disease and dysphagia after continuous subcutaneous injection of MPTP （0.1 mg/kg/d） for 19 days, died 36 days after the injection. ③ The partial symptoms of Parkinson disease after continuous subcutaneous injection of MPTP （0.1 mg/kg/d） for 14 days appeared, and the symptoms were progressively relieved after drug withdrawal until to almost complete regression 60 days after the injection in one animal.④ The irreversible symptoms of Parkinson disease were observed until 60 days after the injection in one animal who received continuous subcutaneous injection of MPTP （0.1 mg/kg/d） for 14 days and then received subcutaneous injection of MPTP （0.1 mg/kg/d） every the other day for 8 days, and survived long. Conclusion The establishment of Parkinson disease model with bilateral chronic irreversible Parkinson disease symptoms, which is similar to the clinical characteristics in the patients with Parkinson disease by subcutaneous injection of appropriate is feasible and reliable in Rhesus Macaques. The monkey may take the initiative in feeding and survive long.

关 键 词：帕金森病 动物模型 猕猴 1-甲基-4-苯基-1 2 3 6-四氢吡啶 皮下注射 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R332[医药卫生—临床医学]