还脑益聪方提取物对淀粉样前体蛋白/早老蛋白1双转基因痴呆模型小鼠学习记忆能力的改善作用及其机制  

Effect and mechanism ofHuannao Yicong decoction extract on learning and memory ability of dementia model of amyloid precursor protein/ presenilin 1double transgenic mice

作　　者：刘美霞[1] 刘剑刚[2] 李浩[1] 刘龙涛[2] 梁琳[1] 胡佳[3] 魏芸[3] 

机构地区：[1]中国中医科学院西苑医院老年病科,北京100091 [2]中国中医科学院西苑医院心血管疾病中心,北京100091 [3]北京化工大学化工资源有效利用国家重点实验室,北京100029

出　　处：《中国药理学与毒理学杂志》2014年第1期10-17,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81173383);国家科技重大专项(2009ZX09103-391)~~

摘　　要：目的探讨还脑益聪方(HYD)提取物改善学习记忆能力的作用机制。方法 3月龄淀粉样前体蛋白(APP)/早老蛋白1(PS1)双转基因小鼠,随机分为模型对照、盐酸多奈哌齐0.65 mg·kg-1、HYD提取物1.7和3.4 g·kg-1组,同龄C57BL/6J小鼠为正常对照。给药组小鼠ig给药,每日1次,连续6个月。给药结束后以跳台实验和Morris水迷宫实验观察小鼠行为变化,HE染色观察小鼠海马CA1区神经元形态变化,实时RT-PCR测定海马组织PS1、热休克蛋白70羧基端作用蛋白(CHIP)、鸟苷酸结合蛋白(CDC42)、呆蛋白(NCT)、激活蛋白-1(AP-1)和活化T细胞核因子(NFAT3)mRNA表达。结果与正常对照组比较,模型组小鼠跳台实验的错误次数增加(P<0.05),潜伏期缩短(P<0.01);水迷宫实验的穿台次数减少(P<0.05),潜伏期延长(P<0.05);海马CA1区神经元数量明显减少,形态结构有所破坏,PS1和CHIP mRNA表达均显著升高(P<0.01)。与模型组比较,跳台实验中多奈哌齐、HYD提取物1.7和3.4 g·kg-1组小鼠的错误次数分别由模型组的5.1±1.2减少至2.2±1.1,2.7±1.2和2.1±1.2(P<0.05),潜伏期由(70±27)s延长至130±33,162±33和(213±38)s(P<0.01);水迷宫实验中小鼠的穿台次数分别由2.1±1.8增加至3.5±1.9,3.6±2.0和3.8±1.8(P<0.05),潜伏期由(139±57)s缩短至95±58,95±58和(94±56)s(P<0.05);海马CA1区神经元数量明显增多,形态较完整;HYD提取物1.7和3.4 g·kg-1可明显降低APP/PS1双转基因小鼠海马PS1 mRNA表达(P<0.05,P<0.01),使CHIP mRNA表达进一步升高(P<0.01),对CDC42,NCT,AP-1和NFAT3 mRNA表达均无明显影响。结论HYD提取物具有提高APP/PS1双转基因小鼠学习记忆能力的作用,该作用可能与其保护神经元和降低PS1mRNA表达有关。OBJECTIVE To investigate the effect and mechanism of Huannao Yicong decoction（ HYD）extract on the learning and memory ability. METHODS The 3-month-old amyloid precursor protein（ APP） /presenilin 1（ PS1） double transgenic mice were randomly divided into four groups： model,donepezil 0. 65 mg·kg^-1,HYD extract 1. 7 and 3. 4 g·kg^-1. Besides,normal C57BL /6J mice of the same age were taken as normal control group. All mice were administered through gastric infusion respectively,once daily for 6 months. The learning and memory ability of mice was observed by the diving platform test and Morris water maze after treatment before being sacrificed. The morphological changes of hippocampal CA1 neurons were observed by HE staining and the mRNA expression of PS1,carboxyl terminus of Hsc70-interacting protein（ CHIP）,GTP binding protein（ CDC42）,nicastrin（ NCT）,activator protein-1（ AP-1） and nuclear factor of activated T cells 3（ NFAT3） in the hippocampus were detected by real time-polymerase chain reaction（ RT-PCR）. RESULTS Compared with the normal group,the wrong number of diving platform tests increased（ P〈0. 05）,while the latency was reduced（ P〈0. 01）; the number of crossing the platform of Morris water maze decreased（ P〈0. 05）,and the latency prolonged（ P〈0.05）; the number of neurons decreased and cellular structure became unclearer in the hippocampal CA1region; the expression of PS1 mRNA and CHIP mRNA increased significantly（ P〈0. 01） in model group. Compared with the model group,in the diving platform test,the wrong number of donepezil,HYD extract 1. 7 and 3. 4 g·kg^-1groups was respectively reduced from 5. 1 ±1. 2 to 2. 2 ±1. 1,2. 7 ±1. 2and 2. 1 ±1. 2（ P〈0. 05）,and the latency prolonged from（ 70 ± 27） s to（ 130 ± 33）,（ 162 ± 33） and（ 213 ±38） s（ P〈0. 01）. In the Morris water maze,the number of crossing the platform of donepezil,HYD extract 1. 7 and 3. 4 g·kg^-1groups respectively increased from 2. 1 ± 1. 8 to 3.

关 键 词：还脑益聪方 淀粉样前体蛋白 早老蛋白1 呆蛋白 小鼠转基因 神经行为学表现 

分 类 号：R285[医药卫生—中药学]