中医药治疗冠状动脉微血管疾病证治规律及作用机制研究

Mechanism of Traditional Chinese Medicine for Treating Coronary Microvascular Diseases

目的:基于文献探讨中医药治疗冠状动脉微血管疾病(CMVD)的证治特征及用药规律,并借助网络药理学和分子对接技术探讨核心药对治疗CMVD的作用机制。方法:系统检索中国知网、万方、维普、中国生物医学文献数据库、PubMed数据库自建库以来至2022年11月1日收录的有关CMVD中医诊治研究的文献,对中医证治规律进行分类统计,并挖掘中药复方的核心药对,利用TCMSP、GeneCards、DisGeNET、TTD、OMIM、STRING、Metascape数据库和Cytoscape软件分析核心药对与疾病间互作关系及相关通路,最后使用分子对接技术对核心化学成分与关键靶点进行对接验证。结果:获得符合要求的文献160篇,CMVD中医证型主要为气虚血瘀证,中药复方涉及药物89味,支持度最高的药对为黄芪-丹参。黄芪-丹参中槲皮素、木犀草素、山柰酚、异鼠李素等成分可通过作用于白细胞介素6(IL6)、胱天蛋白酶3(CASP3)、缺氧诱导因子1A(HIF1A)、过氧化物酶体增殖物激活受体γ(PPARG)等多个靶点影响糖尿病并发症中的晚期糖基化产物(AGE)-晚期糖基化终末产物受体(RAGE)通路、缺氧诱导因子1(HIF-1)通路、核转录因子κB(NF-κB)通路等来干预CMVD。分子对接结果显示核心活性成分与关键靶点对接良好。结论:中医药治疗CMVD多以益气活血法为主,其核心药对黄芪-丹参治疗CMVD的潜在作用机制可能与抗炎症反应、改善氧化应激、调节细胞凋亡相关。

Objective:To explore the characteristics of syndrome and treatment and the rule of drug use of traditional Chinese medicine in treating coronary microvascular disease(CMVD)based on literature,and to explore the mechanism of core drugs for treating CMVD by network pharmacology and molecular docking technology.Methods:CNKI,Wanfang,VIP,China Biomedical Literature Database,and PubMed were retrieved to collect the literature of TCM diagnosis and treatment of CMVD from the establishment of the database to November 1,2022.The classification and statistical analysis of TCM syndromes and treatment principles were conducted,and the core drug pairs were mined.TCMSP,GeneCards,DisGeNET,TTD,OMIM,STRING,Metascape database,and Cytoscape software were used to analyze the interaction between core drug pairs and diseases and related pathways.Finally,molecular docking technology was used to verify the docking between core chemical components and key targets.Results:One hundred and sixty papers were screened to meet the requirements.The TCM syndrome type of CMVD was mainly Qi deficiency and blood stasis,involving 89 drugs.The drug pair with the highest support was Astragalus membranaceus-Salvia miltiorrhiza.Quercetin,luteolin,kaempferol,isorhamnetin and other components in Astragalus membranaceus-Salvia miltiorrhiza can affect advanced glycation endproducts(AGE)-receptor for AGE(RAGE)signaling pathway in diabetic complications,hypoxia-inducible factor(HIF)-1,nuclear factor-κB(NF-κB)and other signal pathways to interfere with CMVD by acting on interleukin 6(IL6),Caspase-3(CASP3),hypoxia-inducible factor 1-alpha(HIF1A),peroxisome proliferator-activated receptor gamma(PPARG),and other targets.The results of molecular docking showed that the key active components were well docked with the target.Conclusion:The treatment of CMVD with traditional Chinese medicine is mainly to invigorate Qi and promote blood circulation.The potential mechanism of its core drug for the treatment of CMVD with"Astragalus membranaceus-Salvia miltiorrhiza"may be related anti-inflammatory reaction,improving oxidative stress,and regulating apoptosis.