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.

Bushen Jiangzhi Formula  /  Atherosclerosis  /  Comprehensive metabolomics  /  Untargeted metabolomics  /  Untargeted lipidomics