首页|补骨脂改善APP/PS1小鼠学习记忆能力的尿液代谢组学研究

补骨脂改善APP/PS1小鼠学习记忆能力的尿液代谢组学研究

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运用尿液非靶代谢组学探究补骨脂改善APP/PS1小鼠学习记忆能力的作用机制.所有动物实验均经过黑龙江中医药大学动物伦理委员会批准(批准号:2020092502).将16只3月龄雄性APP/PS1小鼠随机分为模型组和补骨脂组(0.5 g·kg-1),另取8只同背景C57BL/6J小鼠作为空白组,以避暗实验和新物体识别实验为评价指标,通过超高效液相色谱-四级杆-飞行时间串联质谱(UPLC-Q-TOF-MS)测定各组小鼠尿液中内源性代谢物的变化,筛选差异代谢物,并进行代谢通路富集分析.实验结果显示,与模型组相比,补骨脂可明显减少APP/PS1小鼠的避暗潜伏期及错误次数(P＜0.01),显著提高APP/PS1小鼠的新物体识别指数(P＜0.01).代谢组学分析鉴定出15个差异代谢物,补骨脂能显著回调9个差异代谢物.代谢通路分析显示,组氨酸代谢、柠檬酸循环、牛磺酸和次牛磺酸代谢和糖代谢途径是补骨脂发挥改善学习记忆能力作用的主要代谢途径.研究提示,补骨脂改善APP/PS1小鼠的学习记忆能力的机制可能与改善线粒体功能障碍、降低外周组胺水平、调节能量代谢紊乱及抗氧化水平等相关.
Urine metabolomics study of Psoralea corylifolia in improving learning and memory ability in APP/PS1 mice
Urine nontargeted metabolomics technology was developed for investigating the effect and mecha-nism of improving learning and memory ability in APP/PS1 mice of Psoralea corylifolia.All animal experiments were approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine(Approval No.:2020092502).Sixteen APP/PS 1 mice were randomly divided into the model group and Psoralea corylifolia group(0.5 g·kg-1),and eight male C57BL/6J mice of the same background were selected as control group,step-through test and novel object recognition were used as evaluation indexes.Changes in urine endogenous metabolites of mice from eachgroup were determined by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS),and differential metabolites were screened,and metabolic pathway enrichment analysis was performed.The results of pharmacodynamic investigation showed that Psoralea corylifolia can reduce the dark incubation period and number of errors in APP/PS1 mice(P＜0.01)and improve the new object recognition index of APP/PS1 mice(P＜0.01).Metabolomics analysis identified 15 differential metabolites,and 9 differential metabolites were significantly call back by Psoralea corylifolia.Metabolic pathway analysis showed that histidine metabolism,citric acid cycle,taurine and hypotaurine metabolism and glucose metabolism were the main metabolic pathways of Psoralea corylifolia in improving learning and memory ability.These studies suggest that Psoralea corylifolia improves the learning and memory ability of APP/PS1 mice,and its mechanism may be related to improving mitochondrial dysfunction,reducing peripheral histamine level,regulating energy metabolism disorders and antioxidant levels.

Psoralea corylifolia Linn.Alzheimer's diseasemetabolomicsenergy metabolismAPP/PS1 mice

乔月、薛傲、张悦、徐红丹、李光、赵继会、胡晶、张宁

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黑龙江中医药大学药学院,黑龙江哈尔滨 150040

无锡卫生高等职业技术学校药学系,江苏无锡 214028

中国医学科学院药用植物研究所云南分所,云南景洪 666100

湖南医药学院药学院,湖南怀化 418000

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补骨脂 阿尔茨海默病 代谢组学 能量代谢 APP/PS1小鼠

国家自然科学基金青年基金黑龙江省自然科学基金面上项目黑龙江中医药大学科研项目黑龙江中医药大学科研项目无锡市卫生健康委科研面上项目云南省王金辉专家工作站项目江苏高校"青蓝"工程优秀青年骨干教师培养项目(2022)

82003975LH2020H1012017SEC022015xy04M202170202105AF150057

2024

10.16438/j.0513-4870.2023-0804

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子：1.274
ISSN：0513-4870
年,卷(期)：2024.59(4)
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