基于APP调控探讨补肾化痰益智法对Aβ1-42致AD模型大鼠认知障碍的改善及分子机制  

Effect and Mechanism of Bushen Huatan Yizhi Method on Cognitive Impairment of Alzheimer’s Disease Rats Induced by Aβ Based on APP Regulation

作　　者：林丽[1,2] 杨杰 刘尚志 王平 Lin Li;Yang Jie;Liu Shangzhi;Wang Ping(Cell Biology Lab,College of Basic Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei University of Chinese Medicine,Geriatrics of TCM New Products Collaborative Innovation Center in Hubei Province/Hubei Research Institute of Geriatrics,Wuhan 430065,China;Clinical College of TCM,Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学基础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 [3]湖北中医药大学中医临床学院,武汉430065

出　　处：《世界科学技术-中医药现代化》2021年第5期1355-1361,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(81673856):基于内质网应激及GSK-3β/CREB信号通路探讨补肾化痰益智法对AD样学习记忆损伤的作用机制,负责人:林丽;中国博士后科学基金委员会面上项目(2016M592319):补肾化痰益智法和活血化瘀法防治AD的作用及机制,负责人:林丽。

摘　　要：目的探讨补肾化痰益智法(BSHTYZ)对阿尔茨海默病(Alzheimer’s Disease,AD)样模型大鼠认知障碍的改善及分子机制。方法通过对Sprague Dawley(SD)雄性大鼠侧脑室内注射Aβ1-42构建AD大鼠模型,分别用低(12.5g/kg·d,BSHTYZ-L)、中(25 g/kg·d,BSHTYZ-M)、高(50 g/kg·d,BSHTYZ-H)剂量的补肾化痰益智方水煎液灌胃,分2次灌服,同时设置对照组、模型组和阳性治疗组,4周后利用Morris水迷宫和改良Highman刚果红染色分别观察AD模型大鼠空间学习记忆能力和Aβ在大脑皮层和海马的分布情况,同时利用Western blot检测补肾化痰益智法对AD模型大鼠海马区APP、p APP668及其α、β、γ分泌酶和降解酶IDE等蛋白表达的影响。结果通过大鼠侧脑室注射Aβ1-42,可诱导出大鼠AD样空间学习记忆障碍、大脑皮层和海马的海马Aβ沉积增加及p APP668表达增加,同时可见α分泌酶和IDE降解酶减少、β分泌酶的水平上升,中高剂量的补肾化痰益智方干预后均能显著逆转上述现象,同时高剂量补肾化痰益智方还能降低γ分泌酶的水平。结论补肾化痰益智法能有效改善Aβ1-42引起的AD样模型大鼠的学习记忆能力减退,其保护机制可能通过减少Aβ的生成、增加Aβ的降解从而缓解Aβ在脑内的聚集来调控APP的代谢有关。Objective To study the effect and mechanism of Bushen Huatan Yizhi Method(BSHTYZ) on cognitiveimpairment of the Alzheimer’s Disease(AD) model rats. Methods Alzheimer’s Disease model was established byinjection of β-amyloid protein 1-42(Aβ1-42) in the left lateral ventricles of Sprague Dawley(SD) rats. The rats weretreated with low(12.5 g/kg·d, BSHTYZ-L), medium(25 g/kg·d,BSHTYZ-M) and high(50 g/kg·d, BSHTYZ-H) dose ofprescription of Bushen Huatan Yizhi, then the Morris water maze, modified highman Congo red staining and Westernblot methods were used to detect the ability of learning and memory, the deposition of Aβ and the levels of APP,p APP668, α secretase(ADMA10), β secretase(BACE1), γ secretase(PS1) and insulin degrading enzyme(IDE) in thehippocampus. Results Middle and high doses of prescription of BSHTYZ could effectively reverse the decreased abilityof learning and memory, increase the deposition of Aβ with the level of p APP668 and BACE1, decrease the level ofADMA10 and IDE of the hippocampus induced by Aβ1-42. Conclusion Prescription of BSHTYZ plays a role ofneuroprotection of the cognitive impairment of AD like model of rats induced by Aβ1-42, and the protective mechanismmay be related to the regulation of APP metabolism by reducing the production and increasing the degradation of Aβ toalleviate the aggregation of Aβ in the brain.

关 键 词：补肾化痰益智法 阿尔茨海默症 学习记忆 淀粉样前体蛋白 分泌酶 胰岛素降解酶 

分 类 号：R289.5[医药卫生—方剂学]