实验动物与比较医学 ›› 2019, Vol. 39 ›› Issue (1): 9-14.DOI: 10.3969/j.issn.1674-5817.2019.01.003

• 论著 • 上一篇    下一篇

MPTP诱导树鼩帕金森疾病模型行为学检测方法研究

张志成1,2, 宋庆凯2, 黎晓慧2, 李娜2, 黄鑫1,2, 袁圆2, 王璇2, 李明学2, 代解杰1,2   

  1. 1.昆明医科大学, 昆明 650500;
    2.中国医学科学院/北京协和医学院医学生物学研究所树鼩种质资源中心, 云南省重大传染病疫苗研发重点实验室,中国医学科学院医学生物学研究所实验树鼩标准化与应用研究省创新团队, 昆明 650118
  • 收稿日期:2018-08-30 出版日期:2019-02-25 发布日期:2021-01-29
  • 作者简介:张志成(1986-),硕士,研究方向:人类疾病动物模型的建立及疾病机理研究。E-mail:pathogens@163.com
  • 基金资助:
    云南省联合支持国家计划项目(2015GA009), 云 南省科技人才和平台计划项目(2017HC019), 重点实验室运行补助专项(KF2015-01), 云南省重大 科技专项(2017ZF007)

Behavior Detection Method of MPTP Induced Tree Shrew Parkinson’s Disease Models

ZHANG Zhi-cheng1,2, SONG Qing-kai2, LI Xiao-hui2, LI Na2, YUAN Yuan2, HUANG Xin1,2, WANG Xuan2, LI Ming-xue2, DAI Jie-jie1,2   

  1. 1. Kunming Medical University, Kunming 650500, China;
    2. Center of Tree Shrews Germplasm Resource, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical College, Yunnan Key Laboratory of Major Infections Diseases Vaccine Development, Yunnan Innovation Team of Standardization and Application Research in Laboratory Tree Shrew, Kunming 650118, China
  • Received:2018-08-30 Online:2019-02-25 Published:2021-01-29

摘要: 目的 建立树鼩急性帕金森疾病(PD)模型,对Catwalk、FPA检测系统作为评价PD行为学的方法进行研究。方法 选取14只成年、健康的普通级滇缅树鼩,随机分为模型组(n=10)和对照组(n=4),1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)药物腹腔注射建立急性PD模型,对照组注射等体积0.9%氯化钠溶液。结果 成功建立树鼩急性PD模型。建模1 d后, 与对照组树鼩相比,模型组树鼩空间利用指数下降、低运动性出现次数(BLM)指数显著升高(P均<0.001),表明模型组空间利用能力受损、活动度下降; 模型组右前爪(RF)、左前爪(LF)最大接触面积减少, RF、LF和右后爪(RH)爪印最大接触面积平均压力,以及RF、RH 、LF爪印平均压力及四肢平均力量均下降(P均<0.05),反映了树鼩肌肉僵硬度升高, 可以作为PD步态分析的定量指标; 0~15 Hz(TI1)震颤显著增强(P<0.01), 能较好模拟PD患者静止性震颤的临床表现。结论 MPTP致树鼩急性PD模型能较好模拟PD早期的临床表现。Catwalk、FDA检测系统可提供系统、客观、可靠的PD行为学数据。

关键词: 帕金森疾病, 树鼩, 1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶(MPTP), 动物模型, 行为学, Catwalk步态分析系统, FPA分析系统

Abstract: Objective To establish the acute Parkinson’s disease(PD) model of tree shrew, the Catwalk and force plate actimeter (FPA) detection system was used as a method to evaluate PD behavior. Methods Totally 14 adult conventional grade tree shrew(Tupaia belangeri), weighing (147.6±17.07) g, were randomly divided into model group (n=10) and control group (n=4). The PD model of tree shrews was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) drugs, and control group was injected with equal volume of saline. Results The acute PD model of tree shrews was successfully prepared. Compared with control group, the model group spatial utilization index of tree shrews decreased and the bout of low mobility (BLM) index increased significantly (P all<0.001) after 1 day dosing, indicate that the spatial utilization ability of the model group was impaired and the activity degree was decreased; The maximum contact mean intensity of the right front paws(RF), right hind paws (RH), left front paws (LF). the mean intensity of RF, RH, LF and force average of limbs are decline (P all<0.05).That indicate the increased muscle stiffness of tree shrews, which can be used as a quantitative indicator of PD gait analysis; Tremor indices 1 (0~15 Hz) was significantly enhanced (P<0.01), which could better simulate the clinical manifestations of PD patients with rest tremor. Conclusion MPTP induced tree shrews acute PD model can better simulate the early PD clinical manifestations. Catwalk and FPA analysis systems provide systematic, Objective. and reliable PD behavioral data.

Key words: Parkinson's disease(PD), Tree shrew, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), Animal models, Behavior, Catwalk gait analysis system, Force plate actimeter (FPA)

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