还脑益聪方提取物对APP转基因小鼠脑组织Aβ生成相关因子和学习记忆行为的影响  

Effects of Huannao Yicong Recipe Extract on the Learning and Memory and Related Factors of Aβ Generation in the Brain of APP Transgenic Mice

作　　者：李浩[1] 刘明芳[1] 刘剑刚[1] 刘龙涛[1] 官杰[2] 蔡琳琳[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]山东省青岛市海慈医院集团内分泌科,青岛266033 [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：《中国中西医结合杂志》2013年第1期90-94,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.30873338;No.81173383);国家科技部重大新药创制项目(No.2009ZX09103-391)

摘　　要：目的研究还脑益聪方提取物对β淀粉样前体蛋白(amyloid precursor protein,APP)转基因小鼠学习记忆能力以及脑组织海马CA1区(hippocampal-CA1 area,CA1)APP、淀粉样前体蛋白β位分解酶1(β-site APP-cleaving enzyme,BACE1)、早老素蛋白1(presenilin-1,PS-1)和β淀粉样蛋白(beta amyloid protein,Aβ)的影响,初步探讨还脑益聪方提取物治疗阿尔茨海默病(Alzheimer′sDisease,AD)的作用机制。方法选用3月龄APP695V717I转基因小鼠模型,按数字表法随机分为模型组、盐酸多奈哌齐组、还脑益聪方提取物大剂量组和小剂量组,另设立正常对照组(C57BL/6J小鼠),每组15只。连续灌胃4个月后进行相关指标检测:采用Morris水迷宫观测APP转基因小鼠空间学习记忆行为,采用免疫组织化学法检测APP转基因小鼠海马CA1区APP、BACE1、PS-1和Aβ蛋白的表达水平。结果与正常对照组小鼠比较,7月龄APP转基因模型小鼠在Morris水迷宫实验中穿越原平台位置次数、原平台所在第四象限游泳时间和游泳路程均显著减少(P<0.01);与模型组比较,7月龄盐酸多奈哌齐组、还脑益聪方提取物大、小剂量组小鼠在Morris水迷宫实验中穿越原平台位置次数、第四象限游泳时间和路程均显著增多(P<0.05)。与正常对照组小鼠比较,7月龄模型组小鼠海马CA1区神经元APP、BACE1、PS-1和Aβ阳性表达显著增强(P<0.01)。与模型组比较,7月龄各药物干预组小鼠APP、BACE1、PS-1和Aβ阳性表达显著减弱(P<0.01)。结论还脑益聪方提取物早期应用可明显改善APP转基因小鼠已下降的学习记忆能力,降低海马CA1区神经元APP、BACE1、PS-1和Aβ的表达,减少Aβ生成,延缓APP转基因小鼠大脑病理进程。Objective To study the effects of Huannao Yicong Recipe （HNYCR）extract on the learning and memory ability, and the expressions of amyloid precursor protein （APP）, B-site APP-clea- ving enzyme 1 （BACE1）, presenilin-1 （PS-1）, and beta amyloid protein （Aβ）in hippocampus CA1 area of APP transgenic mice, and to explore its mechanisms for treating Alzheimer＇s disease CAD）. Methods Totally 3-month-old APP695V7171 transgenic mice were used to establish the AD model in this research. They were randomly divided into the model group, the Donepezil group, the large dose HNYCR extract group, the small dose HNYCR extract group, and the normal control group （C57BL/6J mice）, 15 in each group. These animals were gavaged for 4 continuous months. Relevant indicators were detected： Morris water maze test was used to measure the spatial learning and memory ability. The immunohistochemical assay was used to detect the expressions of APP, BACE1, PS-1, and Aβ. Results The times of crossing the original platform and the swimming time and distance in the fourth quadrant of the 7-month-old APP transgenic mice were significantly reduced in Morris water maze test, when compared with the normal con- trol group （P 〈0.01）. The times of crossing original platform and the swimming time and distance in the fourth quadrant of all treatment groups significantly increased in Morris water maze test, when compared with the model group （P 〈0.05）. The expressions of APP, BACE1, PS-1, and Aβ in hippocampus CA1 area of 7-month-old model mice increased significantly （P 〈0.01 ）, when compared with the normal control group. The expressions of APP, BACE1, PS-1, and A~ in each 7-month-old intervention groups were signifi- cantly reduced, when compared with the model group （ P 〈0.01 ）. Conclusion Early application of HNYCR extract can obviously improve the learning and memory ability of APP transgenic mice that has declined, reduce the expressions of APP, BACE1, PS-1, and AI3 in the hippocampal CA1 area, r

关 键 词：阿尔茨海默病 APP转基因小鼠 学习记忆 Β淀粉样蛋白 β位点剪切酶 早老素蛋白-1 还脑益聪方提取物 

分 类 号：R749.16[医药卫生—神经病学与精神病学]