中医药学报2026，Vol.54Issue(2)：6-14,9.DOI:10.19664/j.cnki.1002-2392.260025
补肾降脂方干预Apoe-/-小鼠动脉粥样硬化的全谱代谢组学研究
Full-spectrum Metabolomic Study on the Intervention of Bushen Jiangzhi Formula in Atherosclerosis of Apoe-/-Mice
摘要
Abstract
Objective:To explore the mechanism of Bushen Jiangzhi Formula in intervening atherosclerosis(AS)in Apoe-/-mice based on comprehensive tissue metabolomics.Methods:Apoe-/-mice were fed a high-fat diet to establish an AS model and randomly divided into model(M)group,Bushen(BS)group,and atorvastatin(ATV)group,with age-matched C57BL/6J mice as normal control(C)group.After 12 weeks of intervention,ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)combined with UPLC-Orbitrap mass spectrometry-based untargeted lipidomics was used to detect aortic metabolites and lipids.Bioinformatics analysis was performed to identify signature differential metabolites and lipids.Results:High-fat diet induced typical AS lesions and lipid accumulation in the aortic sinus of Apoe-/-mice.Aortic metabolites were mainly classified as lipids and lipid-like molecules.Compared with the M group,the BS group showed 7 upregulated and 2 downregulated differential metabolites in positive ion mode,and 12 upregulated and 3 downregulated in negative ion mode.Bushen Jiangzhi Formula reversed the expression trends of signature differential metabolites,including deoxythymidine 5'-phosphate(dTMP)and milnacipran.KEGG analysis indicated that dTMP was significantly enriched in the pyrimidine metabolism pathway.Lipidomics identified 3,897 lipid molecules belonging to 44 subclasses.Compared with the M group,the BS group exhibited 102 significantly upregulated and 24 downregulated differential lipid molecules.Bushen Jiangzhi Formula reversed the expression trends of 30 signature differential lipids related to phosphatidylserine(PS),triglyceride(TG),and lysophosphatidylcholine(LPC)subclasses.Correlation analysis revealed strong interrelationships among these signature lipids.Conclusion:The mechanism of Bushen Jiangzhi Formula in intervening AS in Apoe-/-mice may involve regulating aortic metabolite dTMP through the pyrimidine metabolism pathway and modulating the expression of PS-,TG-,and LPC-related lipid molecules at the comprehensive tissue metabolomics level.关键词
补肾降脂方/动脉粥样硬化/全谱代谢组学/非靶代谢组学/非靶脂质组学Key words
Bushen Jiangzhi Formula/Atherosclerosis/Comprehensive metabolomics/Untargeted metabolomics/Untargeted lipidomics分类
医药卫生引用本文复制引用
李琳丹,张悦,邢三丽,申定珠..补肾降脂方干预Apoe-/-小鼠动脉粥样硬化的全谱代谢组学研究[J].中医药学报,2026,54(2):6-14,9.基金项目
国家自然科学基金项目(82074506,81873348) （82074506,81873348）
