中文摘要：

目的：探究16周自主跑轮运动抑制APP/PS1转基因AD小鼠海马Aβ生成的机制。方法：选取C57系APP/PS1转基因小鼠24只,随机分为转基因自主跑轮运动组（TE,n=12）和转基因对照组（TC,n=12）;同时选取C57系野生型小鼠24只,随机分为自主跑轮运动组（E,n=12）和对照组（C,n=12）。TE组和E组小鼠从3月龄开始,除给予正常饮食、饮水,给予16周的自主跑轮运动,TC组和C组小鼠给予正常饮食、饮水,不运动。采用实时荧光定量PCR检测各组小鼠海马β-和γ-分泌酶家族的主要成员BACE1和PS1的mRNA表达水平,并采用Western blot检测各组小鼠海马BACE1、PS1、Aβ40和Aβ42蛋白表达水平。结果：1）16周自主跑轮运动显著性下调了APP/PS1转基因小鼠海马BACE1 mRNA（P〈0.01）和蛋白表达水平（P〈0.01）;2）16周自主跑轮运动显著下调了APP/PS1转基因小鼠海马的PS1蛋白表达水平（P〈0.05）;3）16周自主跑轮运动显著性下调了APP/PS1转基因AD小鼠海马Aβ40（P〈0.05）和Aβ42（P〈0.05）蛋白表达水平。结论：16周自主跑轮运动可通过抑制APP/PS1转基因AD小鼠海马β-和γ-分泌酶基因表达进而抑制Aβ的生成水平。

英文摘要：

Objective： The purpose of this study was to investigate the mechanism of 16 weeks voluntary wheel running inhibiting the hippocampal Aβ production in transgenic mice with Alzheimer＇s disease（ AD）. Methods：Twenty-four male APP / PS1 transgenic mice of line C57 were chosen and divided into transgenic wheel running group（ TE,n = 12） and transgenic control group（ TC,n = 12）. Meanwhile,24 male wild-type mice of line C57 were also chosen and divided into wild-type wheel running group（ E,n = 12） and wild-type control group（ C,n= 12）. Mice in group TE and group E participated in wheel running with diet ad libitum for 16 weeks from 3months old age. Mice in group TC and group C were subjected to food and water ad libitum,without wheel running. The mRNA levels of the main members of β- and γ-secretase,BACE1 and PS1 were detected by RT-PCR.The protein levels of BACE1,PS1,Aβ40 and Aβ42 were tested by Western blot. Results： 1） The 16 weeks wheel running significantly down-regulated the expression of hippocampal BACE1 mRNA（ P〈0. 01） and BACE1protein（ P〈0. 01） in APP / PS1 transgenic mice. 2） The 16 weeks wheel running significantly down-regulated the expression of hippocampal PS1 protein（ P〈0. 05） in APP / PS1 transgenic mice. 3） The 16 weeks wheel running significantly decreased the protein expressions of hippocampal Aβ40（ P〈0. 05） and Aβ42（ P〈0. 05） in APP /PS1 transgenic mice. Conclusions： The 16 weeks wheel running can decrease the generation of Aβ by inhibiting gene expression of β- and γ-secretase in the hippocampus of APP / PS1 transgenic mice.