补肾化痰益智法对阿尔茨海默病模型大鼠学习记忆的影响及机制  

Effect of the Chinese Prescription “Bushen Huatan Yizhi” on Learning and Memory Ability of Rat Model of Alzheimer's Disease

作　　者：林丽 王平 Lin Li Wang Ping(Molecular Cell Biology Lab, College of Basic Medicine Geriatrics of TCM, New Products Collaborative Innovation Center of FIubei Province / Hubei Research Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan 430065, China)

机构地区：[1]湖北中医药大学基础医学院分子细胞生物学实验室,武汉430065 [2]湖北中医药大学老年病中药新产品湖北省协同创新中心/湖北省老年病研究所,武汉430065

出　　处：《华中科技大学学报（医学版）》2017年第5期559-562,570,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81673856;No.81573865);中国博士后科学基金资助项目(No.2016M592319;No.2017T100542);湖北中医药大学青苗计划资助项目(中医校字2015[182]号);湖北中医药大学博士科研项目启动基金资助项目(中医党字[2014]25号)

摘　　要：目的探讨补肾化痰益智法干预阿尔茨海默病(Alzheimer's disease,AD)大鼠模型的效果及机制。方法通过对Sprague Dawley大鼠左侧脑室内注射β-amyloid protein 25-35(Aβ25-35)复制AD大鼠模型,分别用低(12.5g/kg)、中(25g/kg)、高(50g/kg)剂量的补肾化痰益智方水煎液灌胃,2次/d,4周后利用Morris水迷宫和Golgi染色分别观察AD模型大鼠空间学习记忆能力和树突棘的变化,同时利用Western blot检测补肾化痰益智法对AD模型大鼠海马区N-甲基-D-天冬氨酸受体亚单位1(N-methyl-D-aspartate Receptor1,NMDAR1,NR1)和亚单位2B(NR2B)、Syntaxin等蛋白表达的影响。结果通过大鼠左侧脑室注射Aβ25-35,可诱导出大鼠AD样学习记忆能力减退、海马树突棘减少并伴NR2B的水平下降,中剂量的补肾化痰益智方干预后能显著逆转上述效应。结论补肾化痰益智法可逆转Aβ25-35引起的AD样模型大鼠的学习记忆能力衰退,其机制可能与增加神经元树突棘数量并改变其可塑性和上调NR2B水平有关。Objective ＂Bushen Huatan Yizhi＂ is a Chinese prescription that can replenish the kidney,remove phlegm and improve intelligence.This study was aimed to examine the efficacy of＂Bushen Huatan Yizhi＂in the rat model of Alzheimer＇s disease（AD）and the underlying mechanism.Methods The model of AD was established through injection of β-amyloid protein25-35（Aβ25-35）into the left lateral ventricles of Sprague Dawley（SD）rats.Animals were treated with low（12.5g/kg）,medium（25g/kg）or high（50g/kg）dose of＂Bushen Huatan Yizhi＂decotion,twice daily,by gavage.Four weeks later,the Morris water maze and Golgi staining were used to detect the ability of learning and memory and the number of dendritic spines,and Western blotting to measure the levels of N-methyl-D-aspartatic acid receptor1（NR1）,subunit 2B（NR2B）and syntaxin in the left hippocampus.Results Injection ofβ-amyloid protein25-35（Aβ25-35）into the left lateral ventricle of rat could reduce the learning and memory ability of AD rats,which was accompanied by the decrease in the number of dendritic spines and the level of NR2 B.These effects could be reversed by addition of＂Bushen Huatan Yizhi＂at a moderate dose.Conclusion ＂Bushen Huatan Yizhi＂protects against the learning and memory decline of AD rats,possiblely by increasing the number of dendritic spines,regulating their pasticity and upregulating the NR2 Blevel.

关 键 词：补肾化痰益智法 阿尔茨海默病 学习记忆 树突棘 突触蛋白 

分 类 号：R285.5[医药卫生—中药学]