基于UPLC-Q-TOF/MS代谢组学技术的六堡茶改善大鼠动脉粥样硬化作用机制

Mechanisms of Liupao Tea in Ameliorating Atherosclerosis in Rats Based on UPLC-Q-TOF/MS Metabolomics Technology

摘要:

【目的】基于UPLC-Q-TOF/MS代谢组学技术探究六堡茶（Liupao tea，LP）改善大鼠动脉粥样硬化（atherosclerosis，AS）的作用机制。【方法】采用高脂饮食联合腹腔注射维生素D₃的方法诱导AS大鼠模型，设正常对照组、模型组、辛伐他汀组、六堡茶低剂量组、六堡茶高剂量组。干预12周后，通过主动脉、肝脏和结肠的苏木素-伊红（hematoxylin-eosin staining，HE）染色评估组织病理，通过非靶向代谢组学分析尿液差异代谢物，并整合网络药理学筛选活性成分及核心靶标。【结果】六堡茶显著减轻了主动脉中膜增厚、肝脏脂肪变性及结肠损伤。通过代谢组学共鉴定出了379个差异代谢物，六堡茶回调了84.7%异常代谢物，其中血管紧张素Ⅳ和硫酸乙酰肝素均显著上调，富集于肾素-血管紧张素系统、糖胺聚糖降解及癌症中的蛋白聚糖通路；网络药理学分析共筛选出127个活性成分（主要包括多酚类、生物碱类等）及8个核心靶点（MAPK1、MAPK8、MAPK14、BCL2、CASP3、RELA、STAT1、HDAC1），KEGG通路涉及代谢通路、脂质与动脉粥样硬化以及流体剪切应力与动脉粥样硬化等。【结论】六堡茶通过成分-靶点-通路网络协同调节血管功能、抑制炎症氧化应激以及改善代谢紊乱，从而发挥改善AS的作用，为传统茶饮预防AS提供了科学依据。

Abstract:

[Objective] This study aimed to investigate the mechanisms through which Liupao tea (LP) ameliorated atherosclerosis (AS) in rats based on ultra high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) metabolomics technology. [Method] A rat model of AS was established by a high-fat diet combined with intraperitoneal injection of vitamin D ₃. The rats were assigned into the following groups: control, model, simvastatin, low-dose LP, and high-dose LP. After intervention for 12 weeks, histopathological changes in the aorta, liver, and colon were assessed by hematoxylin-eosin (HE) staining. Urinary differential metabolites were analyzed via untargeted metabolomics. Metabolomic findings were integrated with network pharmacology to identify active components and core targets. [Result] LP significantly alleviated aortic medial thickening, hepatic steatosis, and colon injury. Metabolomic analysis identified 379 differential metabolites, among which 84.7% of altered metabolites were reversed by LP. Notably, angiotensin IV and heparan sulfate were significantly upregulated and enriched in the renin-angiotensin system, glycosaminoglycan degradation, and proteoglycan pathway in cancer. Network pharmacology screened out 127 active components (mainly including polyphenols and alkaloids) and 8 core targets (MAPK1, MAPK8, MAPK14, BCL2, CASP3, RELA, STAT1, and HDAC1). KEGG pathway analysis revealed involvement in metabolic pathways, lipid and atherosclerosis, and fluid shear stress and atherosclerosis. [Conclusion] LP ameliorates AS through a component-target-pathway network that collectively modulates vascular function, inhibits inflammation and oxidative stress, and alleviates metabolic disorders. These findings provide a scientific basis for the application of tea in preventing AS.