中国医学科学院学报

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中国医学科学院学报

中国医学科学院学报 ›› 2017, Vol. 39 ›› Issue (2): 240-246.doi: 10.3881/j.issn.1000-503X.2017.02.013

• 论著 • 上一篇    下一篇

脑组织特异表达hS100B转基因小鼠帕金森样运动协调能力改变的初步分析

刘嘉琳1, 郑芳2, 龙彦2, 佟柳2, 郑媛2, 刘小青2, 秦川3()   

  1. 1河北大学医学部病理教研室,河北保定 071000
    2保定市第一中心医院老年病科,河北保定 071000
    3中国医学科学院医学实验动物研究所 北京协和医学院比较医学中心,北京 100021
  • 收稿日期:2016-01-04 出版日期:2017-04-20 发布日期:2017-04-20
  • 作者简介:

    通信作者:秦 川 电话:010-67779915,电子邮件:qinchuan0111@outlook.com

  • 基金资助:
    保定市科学技术研究与发展指导计划(14ZF003)、河北大学医学学科建设基金(2014A1002)和河北大学博士科研启动基金(一省一校专项经费)

Preliminary Analysis of Parkinson-like Motor Coordination Abnormityin Brain-specific hS100B Transgenic Mice

Jialin LIU1, Fang ZHENG2, Yan LONG2, Liu TONG2, Yuan ZHENG2, Xiaoqing LIU2, Chuan QIN3()   

  1. 1Department of Pathology,Hebei University Medical College,Baoding,Hebei 071000,China
    2Department of Geratology,the First Central Hospital of Baoding,Baoding,Hebei 071000,China
    3Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences,Comparative Medicine Center,Peking Union Medical College,Beijing 100021,China
  • Received:2016-01-04 Online:2017-04-20 Published:2017-04-20
  • Supported by:
    Supported by Baoding Sciences and Technology Research and Development Program (14ZF003),Development Fund for Hebei University Medical Science (2014A1002),and Research Fund for the Doctoral Program of Hebei University (Special Funds for A Provincial University)

摘要:

目的 研究S100B在帕金森病发病机制中的作用并探讨脑组织特异表达hS100B转基因小鼠作为帕金森病模型小鼠的可能性。方法 构建hS100B转基因小鼠。小鼠分为S100B转基因组、基因敲除组和阴性对照组。爬杆法和转棒法检测运动协调能力;逆转录-PCR、Western blot对脑组织中S100B、多巴胺D1、D2受体,G蛋白偶联受体激酶2、5及酪氨酸羟化酶的表达进行测定;高效液相色谱-荧光法检测脑组织中酪氨酸、左旋多巴、多巴胺及高香草酸的含量。结果 与阴性对照组相比,转基因组小鼠脑组织中S100B蛋白显著升高(P<0.05),3月龄时可表现出运动协调能力下降,且随着月龄增加,运动协调能力下降呈明显的进行性降低(P<0.05);脑组织中多巴胺D2受体、G蛋白偶联受体激酶2 mRNA和蛋白表达降低(P<0.05);左旋多巴、多巴胺、高香草酸生成增多,高香草酸/多巴胺比值升高(P<0.05);酪氨酸羟化酶的表达虽呈下降趋势,但差异无统计学意义(P>0.05)。S100B基因敲除小鼠脑组织中无S100B蛋白表达,与阴性对照组相比,各检测指标无异常(P>0.05)。结论 S100B很可能是参与帕金森病行为学异常的重要蛋白,脑组织特异表达hS100B转基因小鼠的建立为研究该基因在帕金森病中的作用提供了工具。

关键词: S100B, 帕金森病, 多巴胺受体, G蛋白偶联受体激酶, 多巴胺

Abstract:

Objective To investigate the role of S100B in the development of Parkinson’s disease (PD) and explore the possibility of brain-specific S100B transgenic mice as PD animal model. Methods The hS100B transgenic mice were established. The mice were divided into S100B transgenic group (TG),S100B knockout group (KG),and the non-transgenic control group (CG). Motor coordination ability of mice was measured by the rota-rod and pole-climbing test. The expressions of S100B,dopamine D1 receptor,dopamine D2 receptor,G protein-coupled receptor kinase (GRK)2,GRK5,and tyrosine hydroxylase in brain tissue were detected by reverse transcription-polymerase chain reaction and Western blot. The levels of tyrosine,levodopa,dopamine,and homovanillic acid in brain tissue were measured by high-performance liquid chromatography coupled with fluorescence detection. Results Compared with CG,the S100B protein expression in brain tissue significantly increased in TG (P<0.05);the motor coordination ability of mice showed progressive decline (P<0.05);the mRNA and protein expressions of dopamine D2 receptor and GRK2 significantly decreased (P<0.05);the levels of levodopa,dopamine,and homovanillic acid were significantly elevated (P<0.05);the expression of tyrosine hydroxylase was also down-regulated,although there was no significant difference (P>0.05). Compared with CG,there was no obvious change of the above indicators in KG (all P>0.05). Conclusion S100B plays an important role in the motor coordination abnormity of PD. The brain-specific S100B transgenic mice can be used in research on the role of S100B gene in the development of PD.

Key words: S100B, Parkinson's disease, dopamine receptor, G protein-coupled receptor kinase, dopamine

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