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

发布时间：2018-03-14 22:01

本文选题：SB　切入点：帕金森病　出处：《中国医学科学院学报》2017年02期 　论文类型：期刊论文

【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(P0.05),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(P0.05);脑组织中多巴胺D2受体、G蛋白偶联受体激酶2mRNA和蛋白表达降低(P0.05);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(P0.05);酪氨酸羟化酶的表达虽呈下降趋势,但差异无统计学意义(P0.05)。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(P0.05)。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。
[Abstract]:Objective to study the role of S100B in the pathogenesis of Parkinson's disease and to explore the possibility of brain tissue specific expression of hS100B transgenic mice as Parkinson's disease model mice. Methods hS100B transgenic mice were constructed and divided into S100B transgenic mice. The expression of S100B, dopamine D 1 D 2 receptor, G protein coupled receptor kinase 2 5 and tyrosine hydroxylase in brain tissue was detected by reverse transcriptase (RT PCR) Western blot, and the expression of S100B, dopamine D 1 D 2 receptor, G protein coupled receptor kinase 2 5 and tyrosine hydroxylase were detected by reverse transcriptase (RT PCR) Western blot. The contents of tyrosine, levodopa, dopamine and homovanillic acid in brain tissue were determined by high performance liquid chromatography-fluorescence method. The S100B protein in the brain tissue of transgenic mice increased significantly at the age of 3 months, and the ability of motor coordination decreased with the increase of age. The ability of motor coordination decreased gradually (P 0.05), the expression of dopamine D 2 receptor, G protein coupled receptor kinase 2 mRNA and protein decreased (P 0 05), the levodopa, dopamine and homovanoxalic acid increased, and the expression of dopamine D 2 receptor and G protein coupled receptor kinase 2 mRNA and protein decreased. Although the expression of tyrosine hydroxylase decreased, there was no significant difference in the expression of S100B protein between P0.05S100B knockout mice and negative control group. Conclusion S100B may be an important protein involved in behavioral abnormality of Parkinson's disease. The establishment of hS100B transgenic mice specifically expressed in brain tissue provides a tool for studying the role of S100B in Parkinson's disease.
【作者单位】：河北大学医学部病理教研室;保定市第一中心医院老年病科;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;
【基金】：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);河北大学博士科研启动基金(一省一校专项经费)~~
【分类号】：R742.5

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