还脑益聪方提取物对APP/PS1双转基因小鼠学习认知能力及APP代谢相关蛋白的影响  

Effects of Huannao Yicong Decoction extract on learning and cognitive ability of APP/PS1 double transgenic mice and APP metabolism related protein

作　　者：石丹丹 刘美霞[2,3] 刘剑刚[2] 周丽娟 李浩[3] 魏芸[4] SHI Dan-dan;LIU Mei-xia;LIU Jian-gang;ZHOU Li-juan;LI Hao;WEI Yun(China Academy of Chinese Medical Sciences,Beijing 100700,China;Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Institute of Geriatrics of China Academy of Chinese Medical Sciences,Beijing 100091,China;State Key Laboratory of Chemical Resource Engineering,Beijing University of Chemical Technology,Beijing 100029,China)

机构地区：[1]中国中医科学院,北京100700 [2]中国中医科学院西苑医院,北京100091 [3]中国中医科学院老年病研究所,北京100091 [4]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：《中华中医药杂志》2022年第8期4383-4388,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81173383)。

摘　　要：目的:观察还脑益聪方提取物对APP/PS1双转基因小鼠学习认知能力及APP代谢相关蛋白的影响,探讨其治疗阿尔茨海默病的作用机制。方法:将60只APP/PS1双转基因小鼠随机分为模型组,盐酸多奈哌齐组,还脑益聪方低、高剂量组,每组15只,将同遗传背景的15只C57BL/6J小鼠作为正常组。各用药组均以相应药物灌胃,模型组和正常组给予等体积的蒸馏水灌胃,连续灌胃6个月。Morris水迷宫检测小鼠学习记忆及空间记忆能力;ELISA法检测海马组织APP、Aβ_(1-40)、Aβ_(1-42)含量;Western blot检测海马组织中PS1、CHIP、CDC42及NCT、AP-1、NFAT3蛋白的表达。结果:与正常组比较,模型组小鼠逃避潜伏期显著延长(P<0.05),第四象限游泳时间及路程显著减少(P<0.01),海马组织中APP、Aβ_(1-40)及Aβ_(1-42)含量显著增加(P<0.01),海马组织中PS1、CHIP、CDC42、AP-1、NFAT3蛋白表达均显著升高(P<0.01,P<0.05)。与模型组比较,各用药组小鼠逃避潜伏期显著缩短(P<0.05),还脑益聪方低、高剂量组第四象限游泳时间及路程均显著增加(P<0.05),各用药组APP、Aβ_(1-40)及Aβ_(1-42)含量显著减少(P<0.01,P<0.05);盐酸多奈哌齐组、还脑益聪方高剂量组PS1蛋白表达显著降低(P<0.05),还脑益聪方高剂量组CHIP蛋白表达显著升高(P<0.05)。结论:还脑益聪方提取物可以通过上调CHIP蛋白表达,降低PS1蛋白表达,抑制γ-分泌酶活性,减少APP的裂解和Aβ蛋白生成,从而改善APP/PS1小鼠的学习记忆能力。Objective:To observe the effects of Huannao Yicong Decoction(HYD)extract on the learning and cognitive ability of APP/PS1 double transgenic mice and APP metabolism-related proteins,and to explore the mechanism of HYD in treating Alzheimer’s disease.Methods:A total of 60 APP/PS1 double transgenic mice were randomly divided into model group,donepezil group,HYD low-dose(HYD-L)group and HYD high-dose(HYD-H)group,with 15 mice in each group.A total of 15C57BL/6J mice with the same genetic background were taken as the normal group.Each drug group was given corresponding drugs by gavage.The model group and the normal group were given the same volume of distilled water by gavage for 6 months.The learning and spatial memory function was tested by Morris water maze.The contents of APP,Aβ_(1-40)and Aβ_(1-42)in hippocampus were evaluated by ELISA.The expressions of PS1,CHIP,CDC42,NCT,AP-1 and NFAT3 proteins in hippocampus were detected by Western blot.Results:Compared with the normal group,the escape latency in the model group was significantly prolonged(P<0.05),and the swimming time and distance in the fourth quadrant were significantly reduced(P<0.01),and the contents of APP,Aβ_(1-40)and Aβ_(1-42)in the hippocampus were significantly increased(P<0.01),and the expressions of PS1,CHIP,CDC42,AP-1 and NFAT3 proteins in hippocampus were significantly increased(P<0.01,P<0.05).Compared with the model group,the escape latency in each drug group was significantly shortened(P<0.05),and the swimming time and distance in the fourth quadrant of HYD-L group and HYD-H group were significantly increased(P<0.05),and the contents of APP,Aβ_(1-40)and Aβ_(1-42)in each drug group were significantly reduced(P<0.01,P<0.05);and the expression of PS1 protein in donepezil group and HYD-H group was significantly reduced(P<0.05),and the expression of CHIP protein in the HYD-H group was significantly increased(P<0.05).Conclusion:The HYD extract could significantly improve the learning and memory ability of APP/PS1 mice.The mechanism may be thro

关 键 词：阿尔茨海默病 还脑益聪方 学习记忆 APP/PS1双转基因小鼠 Β-淀粉样蛋白 

分 类 号：R285.5[医药卫生—中药学]