补骨脂改善APP/PS1小鼠学习记忆能力的血清代谢组学研究  

Serum metabolomics study of Psoraleae Fructus in improving learning and memory ability of APP/PS1 mice

作　　者：顾佳明 薛慧 薛傲 姜晶 耿放[3] 赵继会 杨波[1] 张宁[1,2] GU Jia-ming;XUE Hui;XUE Ao;JIANG Jing;GENG Fang;ZHAO Ji-hui;YANG Bo;ZHANG Ning(School of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Jiamusi College,Heilongjiang University of Chinese Medicine,Jiamusi 154007,China;College of Chemistry and Chemical Engineering,Harbin Normal University,Harbin 150025,China;School of Pharmaceutical Sciences,Hunan University of Medicine,Huaihua 418000,China)

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040 [2]黑龙江中医药大学佳木斯学院,黑龙江佳木斯154007 [3]哈尔滨师范大学化学化工学院,黑龙江哈尔滨150025 [4]湖南医药学院药学院,湖南怀化418000

出　　处：《中国中药杂志》2023年第15期4039-4045,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81673581,82174007);中央支持地方高校改革发展资金人才培养项目;黑龙江中医药大学基金项目(2018RCD19,2019BJP01);黑龙江省自然科学基金优秀青年基金项目(YQ2019H001)。

摘　　要：通过血清代谢组学方法探讨补骨脂改善APP/PS1小鼠学习记忆能力的作用机制,筛选补骨脂对APP/PS1小鼠的差异代谢物,并揭示其对APP/PS1小鼠代谢通路的影响。选取30只3月龄的APP/PS1小鼠随机分为模型组和补骨脂提取物组,另取15只同月龄的C57BL/6小鼠作为空白组。采用水迷宫和新物体识别实验评价小鼠学习记忆能力,随后用代谢组学方法对小鼠血清中代谢物进行分析。水迷宫实验结果显示,补骨脂对缩短APP/PS1小鼠的逃避潜伏期效果显著(P<0.01),对增加平台穿越次数和靶向限停留时间效果显著(P<0.01);新物体识别实验结果显示,补骨脂可明显提高APP/PS1小鼠的新物体识别指数(P<0.01)。代谢组学实验筛选出18个血清差异代谢物,其中花生四烯酸、色氨酸、甘油磷脂水平给药后降低,谷氨酰酪氨酸水平给药后上升,涉及的代谢通路包括花生四烯酸代谢、甘油磷脂代谢、色氨酸代谢、亚油酸代谢、α-亚麻酸代谢、甘油脂代谢等。因此补骨脂对APP/PS1小鼠的学习记忆能力具有改善作用,其作用机制可能与促进能量代谢、降低氧化损伤、保护中枢神经系统、减少神经炎症、降低Aβ沉积的作用有关。这将为补骨脂治疗阿尔茨海默病(Alzheimer′s disease,AD)提供帮助,进一步解释其治疗AD的作用机制。This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics,screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice,and reveal its influence on the metabolic pathway of APP/PS1 mice.Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group,and another 15 C57BL/6 mice of the same age were assigned to the blank group.The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests,and metabolomics was used to analyze the metabolites in mouse serum.The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01),and increased the number of platform crossing and residence time in the target quadrant(P<0.01).The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01).Eighteen differential metabolites in serum were screened out by metabolomics,among which the levels of arachidonic acid,tryptophan,and glycerophospholipid decreased after drug administration,while the levels of glutamyltyrosine increased after drug administration.The metabolic pathways involved included arachidonic acid metabolism,glycerophospholipid metabolism,tryptophan metabolism,linoleic acid metabolism,α-linolenic acid metabolism,and glycerolipid metabolism.Therefore,Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to the effects in promoting energy metabolism,reducing oxidative damage,protecting central nervous system,reducing neuroinflammation,and reducing Aβdeposition.This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer′s disease(AD)and further explain the mechanism of Psoraleae Fructus in the treatment of AD.

关 键 词：补骨脂 阿尔茨海默病 代谢组学 能量代谢 APP/PS1 

分 类 号：R285.5[医药卫生—中药学]