基于数据挖掘、网络药理学及分子对接的糖尿病性心脏病用药规律及核心中药分析

Medication rules and core TCM medicine analysis of diabetic heart disease based on data mining,network pharmacology and molecular docking

目的:运用数据挖掘的方法探究中药复方治疗糖尿病性心脏病的用药特点及配伍规律,并运用网络药理学及分子对接探讨高频药物治疗的作用机制,为临床用药提供参考。方法:首先,依据纳入标准和排除标准收集中国知网、维普、万方数据库治疗糖尿病性心脏病的中药处方,将其结果按照统一标准进行规范化处理,运用SPSS Modeler 18.0等软件进行分析。其次,使用中药系统药理学数据库与分析平台(TCMSP)等对高频药物获取化合物对应的靶点,与GeneCards、OMIM、pharmGKB、TTD数据库中检索糖尿病性心脏病相关靶点相互映射并取其交集,通过Cytoscape 3.2.1软件构建“成分-靶点-关键通路”可视化网络分析。通过R语言数据库进行京都基因与基因组百科全书(KEGG)富集分析及基因本体论(GO)富集分析。最后,用SYBYL等软件进行分子对接。结果:共收集401篇文献,纳入198首处方,包含183味中药,使用频次最高依次为丹参(121次)、麦冬(92次)、五味子(77次)、黄芪(76次),关联规则得到支持的较高的组合22个。通过网络药理学方法发现丹参-麦冬-五味子-黄芪的99个活性成分,筛选出10个核心靶点。分子对接表明关键活性成分与核心靶点能够形成稳定的空间结构,其中肿瘤蛋白p53(Tumor Protein p53,TP53)结合能力最强。结论:本研究经数据分析得出,在糖尿病性心脏病的临床治疗中以补虚药、清热药、活血化瘀药为主;多选用药性偏温、平、寒;药味偏甘、苦、辛;归肝、脾、肺、心经的药物,可着重参考麦冬-赤芍、五味子;麦冬-太子参、五味子的配伍。核心中药治疗糖尿病性心脏病是应用槲皮素、豆甾醇、山柰酚、木樨草素、尿苷等活性成分,以TP53、MYC原癌基因(MYC Proto-Oncogene,MYC)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)、信号转导因子和转录激活因子(Signal Transducer and Activator of Transcription,STAT)3等为关键靶点发挥作用,为进一步研究其作用机制提供参考。

Objective:This study uses data mining to explore the drug characteristics and compatibility rules of TCM medicine combination in the treatment of diabetic heart disease,and uses network pharmacology and molecular docking to explore the mechanism of action of high-frequency drug treatment,so as to provide reference for clinical use.Methods:Firstly,the TCM prescriptions for the treatment of diabetic heart disease were collected according to the inclusion criteria and exclusion criteria in CNKI,VIP,Wanfang database,and the results were standardized according to the unified standards,and the software such as SPSS Modeler 18.0 and other software were used for analysis.Secondly,TCMSP and other databases were used to map and intersect diabetic heart disease-related targets retrieved from GeneCards,OMIM,pharmGKB and TTD databases,and the component-target-key pathway visual network analysis was constructed through Cytoscape 3.2.1 software.KEGG enrichment analysis and GO enrichment analysis through R language database.Finally,molecular docking is performed with software such as SYBYL.Results:A total of 401 articles were collected,and 198 prescriptions were included,including 183 flavors of TCM medicine,the highest frequency of use was Danshen(Radix et Rhizoma Salviae Miltiorrhizae)(121 times),Maidong(Radix Ophiopogonis)(92 times),Wuweizi(Fructus Schisandrae Chinensis)(77 times),Huangqi(Radix Astragali)(76 times),and 22 combinations with higher association rules were supported.The 99 active ingredients of Danshen-Maidong-Wuweizi-Huangqi were discovered by network pharmacological methods,and 10 core targets were screened.Molecular docking showed that the key active ingredients and the core target could form a stable spatial structure,among which TP53 had the strongest binding ability.Conclusion:The data analysis of this study shows that in the clinical treatment of diabetic heart disease,deficiency tonic drugs,antipyretic drugs,and blood circulation and stasis drugs are the main drugs.Choose more medicinal properties of temperature,flat and cold.The taste of medicine is sweet,bitter and spicy.Drugs belonging to the liver,spleen,lungs and heart meridians can focus on Maidong-Shaoyao(RadixPaeoniae Rubra)and Wuweizi.Maidong-Taizishen(Radix Pseudstellariae)and Wuweizi.The core TCM for the treatment of diabetic heart disease is the application of quercetin,bean sterol,kaemphol,luteol,uridine and other active ingredients,with TP53,MYC,MAPK,STAT3,etc.as key targets to provide reference for further study of its mechanism of action.