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中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (1): 17-24.doi: 10.10247/j.cjap.6191.2022.004

• 研究论文 • 上一篇    下一篇

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*

郝凯敏, 刘镇, 王浩玉, 祁文秀   

  1. 山西医科大学汾阳学院, 汾阳 032200
  • 收稿日期:2021-04-05 修回日期:2021-11-09 出版日期:2022-01-28 发布日期:2022-05-30
  • 通讯作者: Tel: 0358-2892014; E-mail: fycqwx@163.com
  • 基金资助:
    * 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)

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

HAO Kai-min, LIU Zhen, WANG Hao-yu, QI Wen-xiu   

  1. Fenyang College of Shanxi Medical University, Fenyang 032200, China
  • Received:2021-04-05 Revised:2021-11-09 Online:2022-01-28 Published:2022-05-30

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Aβ1-42、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、Aβ1-42、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Aβ1-42、p-Tau/Tau的表达均呈现逐渐增加,而血液中的Aβ1-42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、Aβ1-42、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。

关键词: 阿尔茨海默病, 淀粉样β蛋白, LRP-1, PTK2B, APP/PS1小鼠

Abstract: 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 Aβ1-42, 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, Aβ1-42, 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, Aβ1-42 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 Aβ1-42 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, Aβ1-42 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.

Key words: Alzheimer's disease, beta amyloid protein, low density lipoprotein receptor-related protein-1, PTK2B, APP/PS1 transgenic mice

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