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HSP90在APP/PS1小鼠海马组织中年龄依赖性表达变化

王冰怡, 刘思钰, 郝凯敏, 祁文秀^*

山西医科大学汾阳学院，汾阳 032200

摘要

本研究旨在观察阿尔茨海默病(Alzheimer's disease, AD)动物模型海马组织中热休克蛋白90 (heat shock protein 90, HSP90)、β-淀粉样蛋白(amyloid-β, Aβ)以及Tau磷酸化水平在不同月龄的变化规律。将6、9、12月龄的APP/PS1转基因小鼠分为3个实验组，同月龄的C57BL/6J小鼠为相应对照组，每组8只。用Morris水迷宫检测各组小鼠的认知行为学能力；Western blot或免疫组织化学检测小鼠海马组织中HSP90、Aβ1-42的表达以及Tau蛋白磷酸化水平；qRT-PCR检测海马组织hsp90 mRNA的表达；尼氏染色检测小鼠海马神经细胞形态和数量的变化。结果显示，APP/PS1转基因小鼠相较于同月龄的C57BL/6J小鼠，其海马组织中HSP90和hsp90 mRNA的表达降低(P < 0.05或P < 0.01)，Aβ1-42和Tau蛋白磷酸化水平则升高(P < 0.05或P < 0.01)；不同月龄的APP/PS1转基因小鼠之间比较后发现，其海马组织中HSP90和hsp90 mRNA表达降低(P < 0.05或P < 0.01)以及Aβ1-42和Tau蛋白磷酸化水平升高(P < 0.01或P < 0.05)均随着月龄的增加呈现进行性发展，同时其认知能力也逐渐减退。以上结果提示，APP/PS1小鼠海马组织中HSP90表达降低、Aβ1-42和Tau蛋白磷酸化水平升高及其认知功能降低均呈现年龄依赖性。

关键词： 阿尔茨海默病; HSP90; APP/PS1小鼠

Age-dependent expression of HSP90 in the hippocampus of APP/PS1 mice 

WANG Bing-Yi, LIU Si-Yu, HAO Kai-Min, QI Wen-Xiu^*

Fenyang College of Shanxi Medical University, Fenyang 032200, China

Abstract

 The present study aims to observe the change in expression of heat shock protein 90 (HSP90) along with amyloid-β (Aβ) and phosphorylated Tau (p-Tau) protein levels in the hippocampus tissue of Alzheimer's disease (AD) transgenic animal model with age. APP/PS1 transgenic mice at age of 6-, 9- and 12-month and C57BL/6J mice of the same age were used. The cognitive abilities of these animals were evaluated using a Morris water maze. Western blot or immunohistochemistry was used to detect the expressions of HSP90 and Aβ1-42, as well as the phosphorylation levels of Tau protein in the hippocampus. The hsp90 mRNA levels and the morphology and number of cells in the hippocampus were detected with real-time quantitative polymerase chain reaction (qRT-PCR) and Nissl staining, respectively. The results showed that compared with C57BL/6J mice of the same age, HSP90 and hsp90 mRNA expression were decreased (P < 0.05 or P < 0.01), while Aβ1-42 and p-Tau protein levels were increased (P < 0.05 or P <0.01) in the hippocampal tissue of APP/PS1 transgenic mice. Meanwhile, the decrease in HSP90 and hsp90 mRNA expression (P < 0.05 or P < 0.01), the increase in Aβ1-42 and p-Tau levels (P < 0.01 or P < 0.05) in hippocampal tissue and the reduction in behavioral ability showed a progressive development with the advancing of age in the APP/PS1 transgenic mice. In conclusion, in the hippocampal tissue of APP/PS1 mice, the decrease in HSP90 expression and the increase in Aβ1-42 and p-Tau levels together with the decline of their cognitive ability are age-dependent. 

Key words: Alzheimer’s disease; heat shock protein 90; APP/PS1 transgenic mice

收稿日期：　　录用日期：

通讯作者：祁文秀　　E-mail: fycqwx@163.com

DOI: 10.13294/j.aps.2024.0014

引用本文：

王冰怡, 刘思钰, 郝凯敏, 祁文秀. HSP90在APP/PS1小鼠海马组织中年龄依赖性表达变化[J]. 生理学报 2024; 76 (2): 257-265.

WANG Bing-Yi, LIU Si-Yu, HAO Kai-Min, QI Wen-Xiu. Age-dependent expression of HSP90 in the hippocampus of APP/PS1 mice . Acta Physiol Sin 2024; 76 (2): 257-265 (in Chinese with English abstract).