二苯乙烯苷对APP转基因小鼠学习记忆能力和脑内β-淀粉样肽表达的影响

Effects of tetrahydroxy-stilbene-glucoside on learning and memory abilities and cerebralβ-amyloid expression in APP transgenic mice

目的:观察从中药何首乌提取的二苯乙烯苷(TSG)对APP转基因小鼠学习记忆能力、β-淀粉样肽(Aβ)和分泌酶的影响。方法:将APP转基因小鼠随机分为模型组,TSG 0．05和0．2 g·kg-1组,同月龄同背景C57BL／6J小鼠为对照组,各组小鼠从4月龄始连续灌胃给药6个月。用morris水迷宫观察小鼠学习记忆能力,用免疫组化法观察小鼠海马APP,Aβ,β位点剪切酶(BACE,即β-分泌酶)和代表γ-分泌酶的早老蛋白-1(PS-1)的表达。结果:10月龄转基因小鼠模型组与正常对照组相比,模型组学习记忆能力明显降低,海马APP,Aβ和PS-1的表达明显增强。TSG能显著改善模型小鼠学习记忆能力,降低脑内APP、Aβ的生成,抑制海马PS-1的表达。在正常对照组、模型组和TSG组之间,β-分泌酶表达没有明显差异。结论:TSG能减少脑内Aβ形成,改善学习记忆能力,作用机理可能与减少APP生成和抑制γ-分泌酶的表达有关。

Objective ： To evaluate from Radix Polygoni Multiflori on learning the effects of tetrahydroxy-stilbene-glucoside （TSG） extracted and memory abilities and β-amyloid （Aβ） expression in APP transgenic mice. Methods： The transgenic mice were randomly divided into model group, TSG 0. 05, 0.2 g. kg-1 group. Normal control adopted the C57BL/6J mice with corresponding age and background. The mice at the age of 4 months were intragastrically administered with TSG or water for 6 months. Morris water maze test was used to measure the learning and memory abilities at the end of the 6-month administration. The mice were also euthanatized to collect cerebral tissues for the measurement of the expression of APP, Aβ,β-site APP cleaving enzyme （BACE,β-secretase） and presenilin-1 （ PS-1 ） in the hippocampus by immuno-histochemistry with image analysis. Results： Compared with the normal group, the model mice significantly showed the decrease in learning and memory abilities and the increase in APP, Aβ and PS-1 （γ-secretase） expressions in hippocampal region at the end of the 6-month course. TSG increased the learning and memory functions, and reduced the APP and Aβ production and inhibited the PS-1 expression. The β-secretase expression at the hippocampal CA1 region showed the non-significant difference among normal control, transgenic model and TGS groups. Conclusion：TSG may decrease Aβ production to improve the learning and memory abilities by inhibiting the generation of APP and the expression of γ-secretase in the APP transgenic mice.