基于代谢组学的中药治疗冠心病血瘀证生物标志物分析

Research Progress of Traditional Chinese Medicine in Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Metabonomics

目的基于代谢组学探讨中药(复方/单味)治疗不同物种冠心病血瘀证所筛选到的差异代谢物,总结中药干预冠心病血瘀证后的生物标志物及相关代谢通路。方法从中国知网、万方数据库、维普数据库、Embase、PubMed、the Cochrane Library、Web of Science数据库中检索中药(复方/单味)治疗冠心病血瘀证的代谢组学研究。对纳入研究的差异代谢物进行汇总,采用HMDB、PubChem-Subs、KEGG对代谢物进行分子注释,对代谢产物路径可视化采用metPA网络软件进行分析。结果共有8篇文献纳入本研究,计算两个物种中重复出现的代谢物后共统计89个差异代谢物主要参与了132条代谢路径。通过通路拓扑分析并对重复出现的代谢通路进行统计后选出了16条P值小于0.05的代谢通路作为中药(复方/单味)治疗不同物种冠心病血瘀证的代谢通路。对于富集于各条差异性代谢通路上的代谢物,在不同研究中重复筛选到的代谢物包括:苯丙氨酸,谷氨酰胺,甘氨酸,柠檬酸盐,胆碱,肌酸,乳酸,葡萄糖,花生四烯酸。结论各项研究中用于冠心病血瘀证治疗的中药(复方/单味)以血府逐瘀汤、桃红四物汤、养心通脉方、苏合香为代表。基于代谢组学的中药(复方/单味)治疗冠心病血瘀证的生物信息学分析显示其作用机制涉及糖代谢、氨基酸代谢、能量代谢、胆碱代谢、脂肪酸代谢等多个方面,基本的三羧酸循环参与其中。总结了包括乳酸、葡萄糖、柠檬酸、花生四烯酸、肌酸、苯丙氨酸、胆碱、谷氨酰胺以及甘氨酸在内的与冠心病血瘀证证候相关的差异代谢物。

Objective Based on metabolomics,it explored the differential metabolites screened by Chinese herbal medicines(compound/single decoction pieces)for the treatment of coronary heart disease with blood stasis syndrome in different species and summarized the biomarkers and related metabolic pathways after the intervention of Chinese herbal medicines.Methods The metabonomics study of traditional Chinese medicine(compound/single decoction pieces)in the treatment of coronary heart disease with blood stasis syndrome was retrieved from CNKI,Wanfang database,VIP database,EMBASE,PubMed,the Cochrane Library and web of science database.The differential metabolites included in the study were summarized.The metabolites were annotated by HMDB,PubChem subs and KEGG,and the metabolite path visualization was analyzed by metPA network software.Results A total of eight publications were included in this study,and a total of 89 differential metabolites were counted after counting the recurring metabolites in both species that were mainly involved in 132 metabolic pathways.Through the analysis of pathway topology and the statistics of repeated metabolic pathways,16 metabolic pathways with P values less than 0.05 were selected as the metabolic pathways of traditional Chinese medicine(compound/single decoction pieces)in the treatment of coronary heart disease with blood stasis syndrome in different species.For the metabolites enriched in various differential metabolic pathways,the metabolites repeatedly screened in different studies included phenylalanine,glutamine,glycine,citric acid,choline,creatine,lactic acid,β-glucose,α-glucose and arachidonic acid.Conclusion The herbs(compound/single decoction pieces)used for the treatment of coronary heart disease with blood stasis syndrome in various studies were represented by Xuefu Zhuyu Decoction(血府逐瘀汤),Taohong Siwu Decoction(桃红四物汤),Yangxin Tongmai Formula(养心通脉方)and Suhexiang(Styrax).Bioinformatics analysis based on metabolomics of Chinese herbal medicines(compound/single decoction pieces)for the treatment of coronary heart disease with blood stasis showed that the mechanism of action involves various aspects of glucose metabolism,amino acid metabolism,energy metabolism,choline metabolism and fatty acid metabolism,in which the basic tricarboxylic acid cycle is involved.The differential metabolites related to coronary heart disease with blood stasis syndrome,including lactic acid,glucose,citric acid,arachidonic acid,creatine,phenylalanine,choline,glutamine and glycine,were summarized.