雷忠义国医大师治疗痰瘀互结...病的用药规律及作用机制探讨_杨波.pdf

世界中西医结合杂志 2023 年第 18 卷第 1 期World Journal of Integrated Traditional and Western Medicine2023，Vol.18，No.1文献研究DOI:10 13935/j cnki sjzx 230105基金项目:国家中医药管理局第三届国医大师/全国名中医传承工作室建设项目国中医药办人教函(2018)119 号;陕西省科技厅重点研发项目(2020SF 345);陕西省中医药管理局项目(2021 GJ LC016)作者单位:1 陕西中医药大学，陕西 咸阳 712046;2 陕西省中医医院，陕西 西安 710003通信作者:陈金锋，Email:cunjin11199991163 com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杨波1石伊娜1陈金锋2【摘要】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A、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A、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。【关键词】冠心病;痰瘀互结;数据挖掘;网络药理学;分子对接【中图分类号】541 4【文献标识码】AMedication egularity and Mechanism by TCM Master Lei Zhongyi in the Treat-ment of Coronary Heart Disease with Phlegm and Blood Stasis SyndromeYANG Bo1，SHI Yi na1，CHEN Jin feng2(1 Shaanxi University of Chinese Medicine，Xianyang Shaanxi 712046;2 Shaanxi Provincial Hospital of Chinese Medi-cine，Xian Shaanxi 710003)【Abstract】ObjectiveTo 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 datamining and network pharmacology MethodsThe TCM prescriptions of Master Lei for the outpatient treatment of coronaryheart disease were collected，and the frequency statistics，association rules，and cluster analysis were carried out on the Tra-ditional Chinese Medicine Inheritance Support System(TCMISS)The core prescriptions were extracted by interviews Themain components and targets of the core prescriptions were screened out by network pharmacology，and the key targets weresubjected to GO and KEGG pathway enrichment analyses Finally molecular docking was performed by computer aidedtechnology for verification esultsSeventy nine TCM prescriptions were screened out by data mining，involving 188drugs The drugs with high frequency included Danshen(Salviae Miltiorrhizae adix et hizoma)，Wuweizi(SchisandraeChinensis Fructus)，and Maidong(Ophiopogonis adix)In terms of drug property and flavor，warm，bitter，and pungentdrugs were dominated After analysis，the core prescriptions were extracted Network pharmacology screened 121 core com-ponents，467 targets，2 802 disease targets，and 248 intersection targets Quercetin，stigmasterol，luteolin，tanshinone A，and sitosterol were found to be the main components in the treatment of coronary heart disease，and the key targets wereAKT1，IL6，TNF，TP53，and VEGFA The main pathways involved lipids and atherosclerosis，fluid shear stress and athero-sclerosis，PI3K Akt，TNF，IL 17，and other signaling pathways Molecular docking results showed that the main compo-nents were relatively stable in binding to the core targets ConclusionIn the treatment of coronary heart disease withphlegm and blood stasis syndrome，Master Lei follows the therapeutic principles of resolving phlegm，diffusing impediment，43世界中西医结合杂志 2023 年第 18 卷第 1 期World Journal of Integrated Traditional and Western Medicine2023，Vol.18，No.1promoting blood circulation，and removing blood stasis，as well as tonifying qi and yin The core prescriptions consist ofDanshen(Salviae Miltiorrhizae adix et hizoma，)Maidong(Ophiopogonis adix)，Wuweizi(Schisandrae Chinensis Fruc-tus)，Sanqi(Notoginseng adix et hizoma)，Chenpi(Citri eticulatae Pericarpium)，and Taizishen(Pseudostellariae a-dix)The mechanism may be attributed to the regulation of the network with core targets of AKT1，IL6，TNF，TP53，andVEGFA by quercetin，stigmasterol，luteolin，tanshinone IIA，sitosterol，etc，to regulate lipids and atherosclerosis，fluidshear stress and atherosclerosis，PI3K Akt，and other signaling pathways【Keywords】Coronary Heart Disease;Phlegm and Blood Stasis;Data Mining;Network Pharmacology;Molecular Docking流行病学显示目前我国冠心病患者大约有1139 万人，但发病率和死亡率仍呈上升趋势，其负担的日益加重正逐渐成为社会公共卫生的主要问题1，2。在当代痰瘀互结已是贯穿冠心病(胸痹心痛)始终的基本病机3，对痰瘀互结型冠心病我们应予以重视。雷忠义国医大师研制的“丹蒌片”已被多指南推荐为治疗痰瘀互结型冠心病的中成药4，5。临床上该类冠心病患者往往兼杂其他症状，单一的成药治疗已不能满足患者需求，需综合多方面考虑，所以学习名家经验和学术思想就显得尤为重要。基于中医传承辅助平台结合网络药理学方法探讨分析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，为提髙中医治疗心系疾病的临床效果提供有益参考，并对新药新方开发予以科学的借鉴。雷忠义(1934 )，男，第三届国医大师、全国首届中医药杰出贡献奖获得者、中国中医科学院首届学部委员、中国中医科学院中医师承制博士生导师;全国第四、六批名老中医药专家学术经验继承导师，陕西省第一、二、五、六批名老中医药专家学术经验继承导师。最早提出心病痰瘀互结理论者之一6。1资料与方法1 1数据挖掘1 1 1处方来源收集 2019 年2021 年就诊于陕西省中医医院心病科雷忠义国医大师门诊冠心病患者的病历资料。1 1 2处方筛选1 1 2 1诊断标准中医诊断标准参考冠心病稳定型心绞痛中医诊疗指南7 和冠心病痰瘀互结证宏观诊断标准研究8，西医诊断标准参考稳定性冠心病诊断与治疗指南9。1 1 2 2纳入标准符合上述诊断标准;处方中含有用药明确中药汤剂处方;临床症状有所改善(参考冠心病痰瘀互结证中医证候评价量表10);病历基本信息完整。1 1 2 3排除标准处方中不含中药汤剂;伴有其他系统严重疾病;孕妇、哺乳期妇女或有生育要求的育龄妇女;病历资料不完整。1 1 3数据录入由专人将筛选后的处方通过中医传承辅助平台(V2 5)临床采集系统录入，录入资料包括:患者姓名、性别、年龄等基本信息，以及就诊后的处方用药、剂量、用法等。参考中