新型微量注射装置在建立帕金森病模型小鼠中的应用  

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

作　　者：左赋兴 苑青 蔡洪庆 韩睿钦 万经海 ZUO Fu-xing;YUAN Qing;CAI Hong-qing;HAN Rui-qin;WAN Jing-hai(Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,CAMS & PUMC, Beijing 100021;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)

机构地区：[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

出　　处：《基础医学与临床》2022年第7期1031-1034,共4页Basic and Clinical Medicine

基　　金：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)。

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。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 experimentalgroup(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.

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 

分 类 号：R-332[医药卫生]