基础医学与临床 ›› 2022, Vol. 42 ›› Issue (7): 1031-1034.doi: 10.16352/j.issn.1001-6325.2022.07.1031

• 研究论文 • 上一篇    下一篇

新型微量注射装置在建立帕金森病模型小鼠中的应用

左赋兴1, 苑青1, 蔡洪庆1, 韩睿钦2*, 万经海1   

  1. 1.国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院 北京协和医学院 肿瘤医院 神经外科,北京 100021;
    2.中国医学科学院基础医学研究所 北京协和医学院基础学院 生物化学与分子生物学系 医学分子生物学国家重点实验室,北京 100005
  • 收稿日期:2022-05-07 修回日期:2022-05-19 出版日期:2022-07-05 发布日期:2022-06-29
  • 通讯作者: * hrq@ibms.pumc.edu.cn
  • 基金资助:
    国家自然科学基金(81701262); 中国医学科学院医学与健康科技创新工程(2020-I2M-C&T-B-071)

Application of a new micro-cannula for the establishment of a Parkinsonian mouse model

ZUO Fu-xing1, YUAN Qing1, CAI Hong-qing1, HAN Rui-qin2*, WAN Jing-hai1   

  1. 1. Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, CAMS & PUMC, Beijing 100021;
    2. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China
  • Received:2022-05-07 Revised:2022-05-19 Online:2022-07-05 Published:2022-06-29
  • Contact: * hrq@ibms.pumc.edu.cn

摘要: 目的 探讨应用改良的小鼠脑内微量注射6-羟基多巴胺(6-OHDA)装置制备稳定帕金森病(PD)模型小鼠的可行性。方法 随机将C57BL/6J雌性小鼠分为实验组(10只)和对照组(10只),实验组应用新型微量注射装置进行单侧纹状体内6-羟基多巴胺(6-OHDA)注射,对照组则使用普通微量注射器。建模后,观测记录小鼠异常行为并统计分析黑质和纹状体组织学改变。结果 旋转实验提示,实验组小鼠均出现阿扑吗啡(Apo)诱导的旋转行为,对照组仅5只小鼠出现旋转行为。建模28 d,对照组小鼠30 min旋转圈数较7 d显著下降(P<0.05),且与实验组差异显著(P<0.05)。免疫组化染色发现,实验组小鼠的黑质多巴胺能神经元较对照组显著减少(P<0.05)。对照组小鼠患侧纹状体内反应性增生的星形胶质细胞增多,部分具有神经前体细胞特征。结论 用于颅内立体定向注射的新型微量注射装置可显著提高制备PD模型小鼠的成功率。

关键词: 帕金森病, 6-羟基多巴胺(6-OHDA), 立体定向框架, 新型微量注射装置, 多巴胺能神经元

Abstract: Objective To explore the feasibility of a modified micro-cannula for intra-cerebral administration of 6-hydroxydopamine(6-OHDA) in order to establish a Parkinsonian mouse model. Methods Twenty female mice(C57BL/6J) were randomly divided into 2 groups with 10 in each: experimental group (new micro-cannula) and control group (regular Hamilton syringe). Following unilateral injection of 6-OHDA, the behavioral test and histological microscopy were performed. Results All mice in experimental group showed the morphology of apomorphine-induced rotational asymmetry, but the same results were found in only 5 mice from control group. Total number of rotations away from the lesion side in 30 minutes showed 6-OHDA-induced motor deficits at day 7 in both groups, which was significantly attenuated at day 28 in control group (P<0.05). After 28 days of 6-OHDA injection, significant reduction in the number of rotations was observed in control mice as compared with that of experimental group (P<0.05). As immunohistochemistry showed that the total number of remaining dopaminergic neurons significantly decreased in the substantial nigra of the experimental mice as compared with the control mice(P<0.05). Moreover, more local astrocytes underwent activation, part of which acquired the properties of neural precursor cells in control mice. Conclusions Intrastriatal injection of 6-OHDA using the new micro-cannula is a feasible technology in the development of a more reliable Parkinsonian model of mice.

Key words: Parkinson's disease, 6-hydroxydopamine(6-OHDA), stereotactic frame, new micro-cannula, dopaminergic neurons

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