雷忠义国医大师治疗痰瘀互结型冠心病的用药规律及作用机制探讨

Medication Regularity and Mechanism by TCM Master Lei Zhongyi in the Treatment of Coronary Heart Disease with Phlegm and Blood Stasis Syndrome

目的基于数据挖掘和网络药理学方法探讨雷忠义国医大师治疗痰瘀互结型冠心病的用药规律及作用机制。方法收集雷忠义国医大师门诊治疗冠心病的中药处方,利用中医传承辅助平台对其进行频数统计、关联规则、聚类分析,结合访谈提取出核心方;采用网络药理学方法筛选出核心方主要成分、关键靶点,并对关键靶点进行GO和KEGG通路富集分析,最后利用计算机辅助技术分子对接进行验证。结果数据挖掘纳入中药处方79个,共涉及药物188味,出现频次较高的药物为丹参、五味子、麦冬等,药性以温性居多,五味以苦味、辛味为主,分析后提取出核心方;网络药理学筛选出核心方药物成分121个、作用靶点467个,疾病靶点2802个,交集靶点248个;发现槲皮素、豆甾醇、木犀草素、丹参酮ⅡA、β-谷甾醇为治疗冠心病的主要成分,关键靶点为AKT1、IL6、TNF、TP53、VEGFA等;主要通路涉及脂质与动脉粥样硬化、流体剪切应力和动脉粥样硬化、PI3K-Akt、TNF、IL-17等信号通路;分子对接结果显示主要成分与核心靶点结合比较稳定。结论雷忠义国医大师治疗痰瘀互结型冠心病以化痰宣痹,活血化瘀为法,同时兼补气阴,其核心方为丹参、麦冬、五味子、三七、陈皮、太子参;其作用机制可能是由槲皮素、豆甾醇、木犀草素、丹参酮ⅡA、β-谷甾醇等主要成分调控AKT1、IL6、TNF、TP53、VEGFA等关键靶点为核心的网络,调控脂质及粥样硬化、流体剪切应力和动脉粥样硬化、PI3K-Akt等信号通路来发挥作用。

Objective To explore the medication regularity and mechanism by traditional Chinese medicine(TCM)master Lei Zhongyi in the treatment of coronary heart disease with phlegm and blood stasis syndrome based on data mining and network pharmacology.Methods The TCM prescriptions of Master Lei for the outpatient treatment of coronary heart disease were collected,and the frequency statistics,association rules,and cluster analysis were carried out on the Traditional Chinese Medicine Inheritance Support System(TCMISS).The core prescriptions were extracted by interviews.The main components and targets of the core prescriptions were screened out by network pharmacology,and the key targets were subjected to GO and KEGG pathway enrichment analyses.Finally molecular docking was performed by computer-aided technology for verification.Results Seventy-nine TCM prescriptions were screened out by data mining,involving 188 drugs.The drugs with high frequency included Danshen(Salviae Miltiorrhizae Radix et Rhizoma),Wuweizi(Schisandrae Chinensis Fructus),and Maidong(Ophiopogonis Radix).In terms of drug property and flavor,warm,bitter,and pungent drugs were dominated.After analysis,the core prescriptions were extracted.Network pharmacology screened 121 core components,467 targets,2802 disease targets,and 248 intersection targets.Quercetin,stigmasterol,luteolin,tanshinoneⅡA,andβ-sitosterol were found to be the main components in the treatment of coronary heart disease,and the key targets were AKT1,IL6,TNF,TP53,and VEGFA.The main pathways involved lipids and atherosclerosis,fluid shear stress and atherosclerosis,PI3K-Akt,TNF,IL-17,and other signaling pathways.Molecular docking results showed that the main components were relatively stable in binding to the core targets.Conclusion In the treatment of coronary heart disease with phlegm and blood stasis syndrome,Master Lei follows the therapeutic principles of resolving phlegm,diffusing impediment,promoting blood circulation,and removing blood stasis,as well as tonifying qi and yin.The core prescriptions consist of Danshen(Salviae Miltiorrhizae Radix et Rhizoma,)Maidong(Ophiopogonis Radix),Wuweizi(Schisandrae Chinensis Fructus),Sanqi(Notoginseng Radix et Rhizoma),Chenpi(Citri Reticulatae Pericarpium),and Taizishen(Pseudostellariae Radix).The mechanism may be attributed to the regulation of the network with core targets of AKT1,IL6,TNF,TP53,and VEGFA by quercetin,stigmasterol,luteolin,tanshinone IIA,β-sitosterol,etc.,to regulate lipids and atherosclerosis,fluid shear stress and atherosclerosis,PI3K-Akt,and other signaling pathways.