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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 被引量:11

Effects of tetrahydroxy-stilbene-glucoside on learning and memory abilities and cerebralβ-amyloid expression in APP transgenic mice
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摘要 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.
出处 《中国新药杂志》 CAS CSCD 北大核心 2006年第7期510-513,共4页 Chinese Journal of New Drugs
基金 国家自然科学基金项目(30472184) 国家重点基础研究发展计划(973计划)项目(2003CB517104) 北京市科技新星计划项目(H020821390190) 首都医学发展基金项目(2002-3002) 北京市自然科学基金资助项目(7032013) 北京市中医药重点学科项目(2005)
关键词 二苯乙烯苷 何首乌 Β淀粉样肽 Γ-分泌酶 APP转基因鼠 阿尔茨海默病 tetrahydroxy-stilbene-glucoside Radix Polygoni Multiflori β-amyloid γ-secretase APP transgenic mice Alzheimer' s disease
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