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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。
AIM: To explore the mechanism of 16-week autonomous run-of-the-ground exercise inhibition of Aβ production in hippocampus of APP / PS1 transgenic AD mice. Methods: Twenty-four C57 APP / PS1 transgenic mice were randomly divided into three groups: untreated group (TE, n = 12) and transgenic control group (TC, n = 12) Twenty - four rats were randomly divided into two groups: spontaneous runner exercise group (E, n = 12) and control group (C, n = 12). The mice in TE group and E group were allowed to run for 16 weeks independently from the normal diet and drinking water. The mice in TC group and C group were given normal diet, drinking water and not exercising. Real-time fluorescent quantitative PCR was used to detect the mRNA expression of BACE1 and PS1 in the hippocampal β-and γ-secretase families. Western blot was used to detect the protein expression of BACE1, PS1, Aβ40 and Aβ42 . Results: 1) 16-week independent runner exercise significantly decreased BACE1 mRNA and protein expression in hippocampus of APP / PS1 transgenic mice (P <0.01); 2) PS1 expression in hippocampus of APP / PS1 transgenic mice (P <0.05); 3) At 16 weeks of independent runner exercise, the levels of Aβ40 (P <0.05) and Aβ42 Protein expression levels. CONCLUSION: Autonomic exercise at 16 weeks can inhibit the production of Aβ by inhibiting the expression of β-and γ-secretase genes in hippocampus of APP / PS1 transgenic AD mice.