基于代谢组学技术分析益气活血中药复方治疗慢性心力衰竭的作用机制

Mechanism of Traditional Chinese Medicine Compound for Benefiting Qi and Activating Blood Circulation for Treating Chronic Heart Failure Based on Metabolomics Technique

目的:基于代谢组学技术探讨益气活血类中药复方治疗慢性心力衰竭所涉及的生物标志物和代谢通路,为慢性心力衰竭中医药治疗的药效评价、不良反应评价以及药代动力学的临床应用提供科学依据。方法:从中国知网、万方、维普、中国生物医学文献服务系统(SinoMed)、PubMed、EMbase、Web of Science核心数据库、the Cochrane Library中检索采用代谢组学方法研究益气活血类中药复方治疗心力衰竭的相关文献。检索时限均为建库至2023年5月,对获得的相关文献进行筛选并提取汇总纳入研究的差异代谢物,采用人类代谢组学数据库(HMDB)、有机小分子生物活性数据(PubChem)、京都基因与基因组百科全书(KEGG)对代谢物进行分子注释,使用Metabo Analyst 5.0网络软件对代谢产物路径进行KEGG富集分析。结果:共纳入11篇文献,涉及中药复方如芪苈强心胶囊、芪参益气滴丸、心阳片、心复康口服液、加参方、益心舒胶囊、七味强心1号,筛选出变量投影重要性(VIP)>1及P<0.05的差异代谢产物共115种,进行通路富集分析发现14条P<0.05的代谢通路,可作为益气活血类中药复方治疗心力衰竭的代谢通路。结论:益气活血类中药复方可改善慢性心力衰竭病人或大鼠的心肌代谢物紊乱,其治疗心力衰竭的作用机制可能与调节氨基酸代谢(如丙氨酸、苯丙氨酸)、糖代谢(如乳酸)、脂代谢(如溶血磷脂酰胆碱、溶血磷脂酰肌醇)及改善心肌能量代谢有关。

Objective:To explore the biomarkers and metabolic pathways involved in the treatment of chronic heart failure by traditional Chinese medicine(TCM)compound for benefiting Qi and activating blood circulation based on metabolomics technique,providing scientific basis for the efficacy evaluation,adverse reaction evaluation and clinical application of pharmacokinetics in the treatment of chronic heart failure with TCM.Methods:The relevant literatures of the treatment of heart failure by compound for benefiting Qi and activating blood circulation were retrieved from China National Knowledge Infrastructure(CNKI)database,Wanfang,VIP,China Biomedical Literature Service System(SinoMed),PubMed,EMbase,Web of Science core database,and the Cochrane Library.The time limit of the search was from the establishment of the library to May 2023.The relevant literature obtained was screened and the differential metabolites included in the study were extracted and summarised,the metabolites were molecularly annotated using Human Metabolome Database(HMDB),PubChem and Kyoto Encyclopedia of Genes and Genomes(KEGG).The metabolites were analysed using the Metabo Analyst 5.0 web software for KEGG enrichment analysis of metabolite pathways.Results:A total of 11 literatures were included,involving Qiliqiangxin Capsules,Qishenyiqi Drops Pills,Xin Yang Tablets,Xin Fukang Oral Liquid,Jia Sheng Formula,Yi Xin Shu Capsules,and Qiweiqiangxin No.1.A total of 115 differential metabolites were screened out with VIP>1 and P<0.05.Pathway enrichment analysis was performed.There were 14 metabolic pathways with P values less than 0.05,which could be used as a beneficial Chinese medicinal herb for the treatment of heart failure.Conclusion:The TCM compound with benefiting Qi and activating blood circulation can significantly improve myocardial metabolite disorders in chronic heart failure patients or rats,and its mechanism of action may be related to the regulation of amino acid metabolism(e.g.,alanine,phenylalanine),glucose metabolism(e.g.,lactic acid),lipid metabolism(e.g.,lysophosphatidylcholine,lysophosphatidylinositol),and the improvement of cardioenergetic metabolism.