基于网络药理学和代谢组学的血脉通胶囊对大鼠急性心肌缺血的保护机制研究。

IF 2.8 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Journal of Chromatography B Pub Date : 2025-01-15 Epub Date: 2024-12-02 DOI:10.1016/j.jchromb.2024.124373
Jialu Zou, Shizhong Zhang, Xiaohong Zhang, Lijuan Xiong, Xuan Chen, Yanmei He, Cancan Duan, Jianyong Zhang
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引用次数: 0

摘要

背景:血脉通胶囊(XMT)是一种被广泛认可的传统苗药,在我国临床广泛应用。已有研究证实XMT对急性心肌缺血(AMI)具有保护作用。然而,XMT为AMI大鼠提供保护的机制尚不完全清楚。研究目的:本研究旨在通过网络药理学、传统药效学和代谢组学研究XMT对AMI大鼠的保护作用机制。材料与方法:应用中药系统药理学和中药分子机制生物信息学分析工具,鉴定XMT的成分和潜在靶点。我们构建了草药-成分-靶点网络,并分析了蛋白质-蛋白质相互作用(PPI)网络。通过途径富集分析探讨了其潜在机制。随后,结扎左冠状动脉前降支建立AMI模型,通过心肌酶谱、心电图、三苯四唑氯(TTC)染色、苏木精-伊红(HE)染色评价XMT对AMI大鼠的保护作用。采用基于UHPLC-Q-Exactive Orbitrap MS的代谢组学方法观察XMT对AMI患者血清代谢谱的保护作用,并通过多元统计分析进一步揭示XMT治疗后代谢物的差异规律。最后进行综合通路分析,揭示生物代谢机制。结果:XMT共392种有效成分作用于624个靶点。通路富集分析显示XMT可通过TNF、MAPK和PI3K-Akt信号通路治疗AMI。此外,XMT能有效预防心电st段抬高,减小心肌梗死面积,降低心脏重量指数和心肌酶水平,减轻AMI大鼠心脏组织损伤。此外,XMT回调117种代谢物和4种代谢途径,包括牛磺酸和次牛磺酸代谢、苯丙氨酸代谢、嘧啶代谢和视黄醇代谢。结合网络药理学和代谢组学,探讨XMT治疗AMI的生物学机制。推测XMT的机制是调节TNF信号通路、PI3K-Akt通路和MAPK信号通路,参与细胞凋亡、氧化应激、免疫和炎症反应等生物学过程。结论:XMT通过调节多种代谢标志物、多种靶点和途径,对AMI大鼠具有保护作用。因此,XMT可能为AMI的治疗提供一种潜在的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Study on the protective mechanism of Xuemaitong Capsule against acute myocardial ischemia rat based on network pharmacology and metabolomics.

Background: Xuemaitong Capsule (XMT) is a widely recognized traditional Miao medicine extensively utilized in Chinese clinical settings. Previous studies have demonstrated XMT protective effects against acute myocardial ischemia (AMI). However, the mechanism by which XMT provides protection to AMI rats is yet to be fully understood.

Aim of the study: The purpose of this study was to investigate the protective mechanism of XMT on AMI rats through network pharmacology, traditional pharmacodynamics and metabolomics.

Material and methods: The components and potential targets of XMT were identified through the application of traditional Chinese medicine system pharmacology and traditional Chinese medicine molecular mechanism bioinformatics analysis tools. We constructed herb-composition-target networks and analyzed protein-protein interaction (PPI) networks. The potential mechanism was explored by pathway enrichment analysis. Subsequently, the AMI model was constructed by ligation of the anterior descending branch of the left coronary artery, and XMT protective effects on AMI rats were evaluated by analyzing the myocardial enzyme profiles, electrocardiograms(ECG), Triphenyltetrazolium chloride(TTC) staining, and Hematoxylin-Eosin (HE) staining in AMI rats. Metabolomics based on UHPLC-Q-Exactive Orbitrap MS was used to observe the protective effect of XMT on the serum metabolic profile of AMI, and multivariate statistical analysis further revealed the differential patterns of metabolites after XMT treatment. Finally, integrated pathway analysis was carried out to reveal the biological metabolic mechanism.

Results: A total of 392 active components of XMT acted with 624 targets for treating AMI. Pathway enrichment analysis revealed that XMT could treat AMI through TNF, MAPK and PI3K-Akt signaling pathways. Further, XMT could effectively prevent ST-segment elevation in the ECG, reduce the size of myocardial infarction, decrease cardiac weight index and cardiac enzyme levels, and mitigate histological damage in the hearts of AMI rats. In addition, XMT callback 117 metabolites and four metabolic pathways, including taurine and hypotaurine metabolism, phenylalanine metabolism, pyrimidine metabolism and retinol metabolism. Through integrating network pharmacology and metabolomics, we explored the biological mechanism by which XMT treats AMI. It was speculated that the mechanism of XMT is to regulate TNF signaling, PI3K-Akt pathway and MAPK signaling pathway, and participate in cell apoptosis, oxidative stress, immune and inflammatory reaction and other biological processes.

Conclusion: XMT plays a protective role in AMI rats by regulating multiple metabolic biomarkers, multiple targets and pathways. Therefore, XMT may provide a potential strategy for the treatment of AMI.

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来源期刊
Journal of Chromatography B
Journal of Chromatography B 医学-分析化学
CiteScore
5.60
自引率
3.30%
发文量
306
审稿时长
44 days
期刊介绍: The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.
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