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黄芪总苷防治地塞米松诱导小鼠记忆障碍和对APP及β-分泌酶mRNA表达的研究
引用本文:张文,李维祖,李卫平,孙翔翔,周素素,徐小群.黄芪总苷防治地塞米松诱导小鼠记忆障碍和对APP及β-分泌酶mRNA表达的研究[J].中国中药杂志,2010,35(5):642-646.
作者姓名:张文  李维祖  李卫平  孙翔翔  周素素  徐小群
作者单位:安徽医科大学,药理学教研室,安徽,合肥,230032
基金项目:安徽省高校省学术带头人科学研究项目(2005hbz18);安徽省人才基金项目(2007Z030) ;安徽省教育厅自然科学重点项目(KJ2009A81)
摘    要:目的:探讨黄芪总苷(AST)对地塞米松(DEX)诱导小鼠记忆障碍的保护作用及对脑内淀粉样前体蛋白(APP)及其mRNA,α-分泌酶和β-分泌酶mRNA表达的影响.方法:将小鼠随机分成6组:正常对照组、模型组、AST(10,20,40 mg·kg~(-1))组和阳性药(人参皂苷Rg_1,6.5 mg·kg~(-1))组.用DEX(5 mg·kg~(-1),ig,21 d)建立小鼠学习记忆损伤模型,各用药组于造模同时ig给予相应药物,模型组和对照组ig等容积蒸馏水.用Morris水迷宫方法测定小鼠学习记忆功能;用RT-PCR方法检测脑组织中APP、α-分泌酶和β-分泌酶mRNA表达;用免疫组织化学方法观察大脑皮质,海马CA1,CA3区APP表达.结果:与模型组比较,AST(20,40 mg·kg~(-1))能明显改善小鼠记忆功能(P<0.05,P<0.01);降低脑组织内APP,β-分泌酶mRNA的表达(P<0.05),升高脑组织内α-分泌酶mRNA的表达(P<0.05);减少APP在大脑皮质及海马CA1区的表达(P<0.05).结论:AST能改善DEX诱导的小鼠记忆障碍,其机制可能与抑制脑内APP及其mRNA、β-分泌酶mRNA表达,促进α-分泌酶mRNA表达有关.

关 键 词:黄芪总苷  糖皮质激素  记忆障碍  淀粉样前体蛋白  α-分泌酶  β-分泌酶
收稿时间:2009/6/25 0:00:00

Study on preventative and curative effects of astragaloside (AST)on mice memory impairment and expression of amyloid precursor proteinand beta secretase mRNA induced by dexamethasone
ZHANG Wen,LI Weizu,LI Weiping,SUN Xiangxiang,ZHOU Susu and XU Xiaoqun.Study on preventative and curative effects of astragaloside (AST)on mice memory impairment and expression of amyloid precursor proteinand beta secretase mRNA induced by dexamethasone[J].China Journal of Chinese Materia Medica,2010,35(5):642-646.
Authors:ZHANG Wen  LI Weizu  LI Weiping  SUN Xiangxiang  ZHOU Susu and XU Xiaoqun
Affiliation:Department of Pharmacology, Anhui Medical University, Hefei 230032, China;Department of Pharmacology, Anhui Medical University, Hefei 230032, China;Department of Pharmacology, Anhui Medical University, Hefei 230032, China;Department of Pharmacology, Anhui Medical University, Hefei 230032, China;Department of Pharmacology, Anhui Medical University, Hefei 230032, China;Department of Pharmacology, Anhui Medical University, Hefei 230032, China
Abstract:Objective :To study the protective effects of astragaloside (AST) on memory impairment and the expression levels of amyloid precursor protein (APP) and its mRNA, alpha secretase and beta secretase mRNA in the brain of mice induced by dexamethasone (DEX). Method : Mice were randomly divided into six groups: control group,model group,AST(10,20,40 mg·kg-1) groups and ginsenoside Rg1 (6.5 mg·kg-1)group. The animal models of dysmnesy mice were established by intragastrical administration of DEX (5 mg·kg-1) for 21 days. Subsequently, the dysmnesy mice were treated by intragastrical administration of ginsenoside Rg1 and different doses of AST(10,20,40 mg·kg-1), respectively. Morris water maze was applied to evaluate the learning and memory function in mice. The expression of APP, alpha secretase and beta secretase mRNA were analysesed by RT-PCR, and immunohistochemistry was used to evaluate the expression levels of APP in cerebral cortex, hippocampus CA1 and CA3. Result : AST(20,40 mg·kg-1) could improve the learning and memory function in mice(P<0.05, P<0.01), decrease the expression levels of APP and beta secretase mRNA(P<0.05), increase the expression level of alpha secretase mRNA(P<0.05), and decrease the expression level of APP in cerebral cortex and hippocampus CA1(P<0.05). Conclusion : AST could improve the learning and memory function in mice, which mechanism may contribtuted to the expression inhibition of APP and APP mRNA, beta secretase mRNA, and promotion of the expression of alpha secretase mRNA.
Keywords:astragaloside  glucocorticoids  dysmnesy  amyloid precusor protein  alpha secretase  beta secretase
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