PTK2B与Aβ、Tau和LRP-1在APP/PS1小鼠海马组织和血液中的表达随月龄变化的分析  

Time dependent expression profiling of PTK2B and its relationship with Aβ,Tau and LRP-1 in hippocampus and blood of APPswe/PS1dE9 double-transgenic mouse

作　　者：郝凯敏 刘镇 王浩玉 祁文秀[1] HAO Kai-min;LIU Zhen;WANG Hao-yu;QI Wen-xiu(Fenyang College of Shanxi Medical University,Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院,汾阳032200

出　　处：《中国应用生理学杂志》2022年第1期17-24,共8页Chinese Journal of Applied Physiology

基　　金：山西省自然科学基金(201801D121348);山西医科大学汾阳学院的科学研究(2020B02)。

摘　　要：目的:探讨阿尔茨海默病(AD)转基因动物模型脑组织中ptk2b基因及其表达产物PTK2B蛋白随着月龄的变化规律,及其与血液和脑组织中Aβ_(1-42)、Tau蛋白磷酸化和LRP-1含量的关系。方法:设5月龄、10月龄、15月龄的APP/PS1转基因小鼠3个实验组,和同月龄的C57BL/6J小鼠3个对照组,共计6组,每组各8只。用Morris水迷宫检测各组小鼠的认知行为学能力,免疫组织化学、Western blot或ELISA检测小鼠海马组织或血液中PTK2B、Aβ_(1-42)、p-Tau/Tau和LRP-1的表达,qRT-PCR检测海马ptk2b mRNA的表达。结果:各实验组结果显示,APP/PS1转基因小鼠随着月龄的增长海马组织中PTK2B、ptk2b mRNA和Aβ_(1-42)、p-Tau/Tau的表达均呈现逐渐增加,而血液中的Aβ_(1-42)则逐渐降低;海马组织中LRP-1表达也逐渐下调,同时,小鼠的认知行为学功能则表现为时间依赖性降低(P均<0.05)。各对照组之间比较,除海马组织中LRP-1随着年龄增加而降低(P<0.05)以外其余指标均没有明显差异(P>0.05)。结论:APP/PS1转基因小鼠海马组织中PTK2B、Aβ_(1-42)、p-Tau/Tau的表达上调和LRP-1下调,与其认知功能降低均呈现时间依赖性变化。Objective:To uncover the time-dependent expression pattern of ptk2b gene and ptk2b-encoded protein,protein tyrosine kinase 2 beta(PTK2B),in the brain tissues of transgenic animal models of Alzheimer’s disease(AD)and its relationship with the levels of Aβ_(1-42),phosphorylation of Tau(p-Tau)and low density lipoprotein receptor-related protein-1(LRP-1)in blood and brain tissues.Methods:In this study,5-,10-and 15-month-old APPswe/PS1dE9 double-transgenic mice harboring the genotype of AD confirmed by the gene test were divided into the 5-,10-and 15-month-old experiment groups,and simultaneously,age-matched C57BL/6J mice were placed into the corresponding control groups,with 8 mice in each group.All mice were subjected to the Morris Water Maze for test of cognitive and behavioral ability.Expression profiles of PTK2B,Aβ_(1-42),p-Tau/Tau and LRP-1 in the hippocampus or blood of mice were quantified by using the immunohistochemistry staining,Western blot or enzyme-linked immunosorbent assay(ELISA),while the mRNA expression of ptk2b in the hippocampus was quantified by using the real-time quantitative polymerase chain reaction(qRT-PCR).Results:Results of experiment groups demonstrated that as mice aged,the expression levels of PTK2B,ptk2b mRNA,Aβ_(1-42) and p-Tau/Tau in the hippocampus were increased,and the expression of LRP-1 was decreased gradually.While in the blood,the level of Aβ_(1-42) was decreased,and the cognitive and behavioral ability was decreased in an age-dependent manner(all P<0.05).However,comparisons among the control groups,only the age-dependent downregulation of LRP-1 were observed in hippocampus(P<0.05),but other indicators had no significant differences(P>0.05).Conclusion:In the hippocampus of APP/PS1 double-transgenic mice,the expressions of PTK2B,Aβ_(1-42) and p-Tau/Tau are upregulated,LRP-1 is downregulated,while cognitive and behavioral ability is decreased,and such changes are presented in a time-dependent manner.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 LRP-1 PTK2B APP/PS1小鼠 

分 类 号：R742[医药卫生—神经病学与精神病学]