基于整合用药网络与靶点网络中药治疗糖尿病合并冠心病核心处方及作用机制探讨

Core prescriptions and mechanism analysis of Chinese medicine for treatment of diabetes mellitus combined with coronary heart disease by integrating medication network and target network

目的整合用药网络与靶点网络方法分析文献中治疗糖尿病合并冠心病方剂的核心处方及药理机制,为今后的实验研究和临床应用提供一种新的思路。方法检索中文文献来源于中国学术期刊全文数据库(CNKI)、万方数据库(Wanfang Data)、维普生物医学数据库(VIP)、中国生物医学文献数据库(SinoMed)、web of science、PubMed、Embase、Cochrane Library中收录治疗糖尿病合并冠心病的相关文献中的方剂,建立处方-药物数据库。运用古今医案平台(V2.3.5)进行频次统计、性味归经分析、关联分析和复杂网络分析,寻求核心处方。利用Cytoscape 3.9.1软件构建靶点网络。将有效靶点导入STRING数据库,构建蛋白质相互作用(PPI)网络分析;利用Metascape数据库进行基因本体(GO)注释及京都基因与基因组百科全书(KEGG)通路富集分析。结果整理后共得到方剂295首,涉及中药204味,其中频次>20次的中药35味,用药频次最高的是丹参;关联规则发现药对黄芪→丹参和黄芪→麦冬的支持度最高;根据频数分析、关联分析、复杂网络分析结果以及临床用药经验,总结出治疗糖尿病合并冠心病的核心处方:丹参、黄芪、麦冬、川芎、五味子、瓜蒌、当归、茯苓。现代中药化学成分研究发现该核心处方的关键成分为槲皮素、黄芪紫檀烷苷、山柰酚、木犀草素等,核心靶点AKT1、TP53、IL-6、CASP3、VEGFA、ESR1、HSP90AA1、EGFR、PPARG、STAT3等。GO功能富集通路为激活剂结合等,KEGG富集通路主要为PI3K-Akt信号通路等。结论通过数据挖掘,得出文献中治疗糖尿病合并冠心病的核心处方组成为丹参、黄芪、麦冬、川芎、五味子、瓜蒌、当归、茯苓,其核心成分为槲皮素、黄芪紫檀烷苷、山柰酚等,这些成分通过PI3K-Akt信号通路作用于AKT1、TP53、IL-6、CASP3、VEGFA、ESR1等靶点,为糖尿病合并冠心病的科学研究和临床治疗提供思路。

Objective Integrating drug network and target network approaches to analyze the core prescriptions and pharmacological mechanisms of prescriptions for the treatment of diabetes mellitus combined with coronary heart disease in the literature,providing a new way of thinking for future experimental studies and clinical applications.Methods The prescriptions in the literature related to the treatment of diabetes mellitus combined with coronary heart disease were searched in CKNI,VIP,Wanfang,SinoMed,web of science,PubMed,Embase and Cochrane Library to build a prescription-drug database.The Ancient and Modern Medical Case Platform(V2.3.5)was used to find the core prescriptions by conducting frequency statistics,nature and flavor attribution analysis,association analysis and complex network analysis.Target networks were constructed using Cytoscape 3.9.1 software.The validated targets were imported into the STRING database to construct protein interaction network analysis.GO enrichment analysis and KEGG pathway enrichment analysis were carried out using the Metascape database.Results After collation,a total of 295 prescriptions were obtained,involving 204Chinese medicines,of which 35 were used more than 20 times,and the most frequent one was Salviae Miltiorrhizae Radix et Rhizoma,the association rule found the highest support for Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and Astragali RadixOphiopogonis Radix.Based on the results of frequency analysis,association analysis,complex network analysis and clinical experience in using medicines,the core prescriptions for treating diabetes combined with coronary heart disease were summarized as Salviae Miltiorrhizae Radix et Rhizoma,Astragali Radix,Ophiopogonis Radix,Chuanxiong Rhizoma,Schisandrae Chinensis Fructus,Trichosanthis Fructus,Angelicae Sinensis Radix,and Poria.The key components of this core prescription were found to be quercetin,(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol,kaempferol,luteolin,etc.The core targets were AKT1,TP53,IL-6,CASP3,VEGFA,ESR1,HSP90AA1,EGFR,PPARG,STAT3,etc.The GO functional enrichment pathway were activator binding,etc.,and the main KEGG enrichment pathways were the PI3K-Akt signaling pathway,etc.Conclusions Through data mining,it was concluded that the core prescription composition in the literature for the treatment of diabetes combined with coronary heart disease is Salviae Miltiorrhizae Radix et Rhizoma,Astragali Radix,Ophiopogonis Radix,Chuanxiong Rhizoma,Schisandrae Chinensis Fructus,Trichosanthis Fructus,Angelicae Sinensis Radix,and Poria.Their core components are quercetin,astragalus purpureus and kaempferol,which act on AKT1,TP53,IL-6,CASP3,VEGFA,ESR1 and other targets through PI3K-Akt signaling pathway,providing ideas for scientific research and clinical treatment of diabetic combined with coronary heart disease.