基于"病-症-方-药"关联分析吴茱萸的妇科用药规律研究OA
Prescription regularity of Wuzhuyu-containing medicines in TCM gynecology based on the association rule analysis of"disease-syndrome-prescription-medicine"
目的:系统整理和挖掘吴茱萸在妇科用药中的规律,为吴茱萸的合理用药和新药研究提供数据支持和方向参考.方法:以"吴茱萸""妇科"及妇科具体病症等为关键词,检索《中医方剂大辞典》、中医方剂数据库、中医世家、中医资源网、中国知网及万方等数据库,根据纳入和排除标准整合相关方剂数据信息,标准化后采用 Microsoft Excel 2019 建立数据库,采用SPSS Modeler 18.0 和 SPSS Statistics 22.0 等统计分析工具进行"病-症-方-药"关联分析,从主治病症、用量、用法、炮制、配伍等多角度对分析结果进行用药规律挖掘和可视化.在中药系统药理学数据库与分析平台、Swiss 数据库及 PharmMapper 中获得吴茱萸活性成分和靶点,在 GeneCards 数据库中获得疾病靶点,筛选交集靶点,使用 Cytoscape 3.9.0 软件构建吴茱萸-疾病-靶点之间的网络图.借助 DAVID 数据库对交集靶点进行基因本体论富集分析和京都基因与基因组百科全书通路分析.将交集靶点导入 STRING 数据库构建蛋白质-蛋白质相互作用网络图,并运用 Cytoscape 3.9.0 进行可视化分析.结果:共纳入相关方剂 296 首,涉及病症 53 种.与吴茱萸配伍的高频中药主要包括当归、桂枝、川芎、姜、人参等,以补虚和活血化瘀药为主,药味多为辛、甘、苦,药性温、平居多,主归脾经、心经、肾经,主治病症以腰、脐、腹痛和月经不调最为常见,吴茱萸用量通常在100 g以下,多超过药典规定剂量;"吴茱萸-当归-桂枝"为核心配伍药对.通过富集分析得到的关键通路有磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)-蛋白激酶 B(Akt)信号通路、晚期糖基化终末产物(advanced glycation end product,AGE)-晚期糖基化终末产物受体(advanced glycation end product receptor,RAGE)信号通路、内分泌抵抗信号通路等,通过蛋白质-蛋白质相互作用网络分析得到的关键靶点有丝氨酸/苏氨酸蛋白激酶 1、信号转导和转录活化因子 3、雌激素受体 1 等.结论:中医妇科中,吴茱萸配伍药对以补虚药为主,主要针对月经不调、腹痛等病症,治法以补法为主,用法、炮制等以减毒为主要目的,与当归、人参、生姜等药之间可能存在配伍增效减毒作用,并通过网络药理学研究其活性成分、靶点和相关信号通路.本研究可为吴茱萸临床妇科安全合理用药提供依据,并为推动吴茱萸药典标准提升、基于"效-毒"关联评价的配伍及方剂研究提供方向参考.
Objective:Systematically summarize the prescribing regularity of Wuzhuyu(Fructus Evodiae)in gynecology of traditional Chinese medicine(TCM)to provide data support and direction reference for rational drug use and new drug research.Methods:Using"Wuzhuyu""gynecology",and specific diseases and syndromes as keywords,databases including the Dictionary of Chinese Medical Formulas,Traditional Chinese Medicine Classic Prescriptions database,Traditonal Chinese Medicine Heritage Family,Traditional Chinese Medicine Resource Network,CNKI,Wanfang Medical Network were searched.According to the inclusion and exclusion criteria,the relevant prescription data information was integrated,and Microsoft Excel 2019 was used to establish the database after standardization.Statistical analysis tools such as SPSS Modeler 18.0 and SPSS Statistics 22.0 were used to conduct the association analysis of"disease-syndrome-prescription-medicine",and the analysis results were mined and visualized from the perspectives of main disease syndrome,dosage,usage,processing and compatibility.Active ingredients and targets of Wuzhuyu were obtained in TCMSP,Swiss database,and PharmMapper database.Diseases targets were obtained from GeneCards database,and overlapping targets were screened out.Cytoscape 3.9.0 software was used to map the Wuzhuyu-diseases-target protein network.GO enrichment analysis and KEGG pathway analysis were performed on intersection targets by DAVID.Intersection targets were imported into the STRING database to obtain a protein-protein interaction network diagram,and Cytoscape 3.9.0 was used for visualization and screening of core targets.Results:A total of 296 relevant prescriptions were included,involving 53 kinds of diseases and syndromes.Among them,the high-frequency compatible herbs were mainly Danggui(Radix Angelicae Sinensis),Guizhi(Ramulus Cinnamomi),and Chuanxiong(Rhizoma Ligustici Chuanxiong).The main types of herbs were stasis-removing and blood-activating herbs.The main flavors were pungent,sweet and bitter and the main natures were warm and neutral.According to meridian tropism,the herbs mainly entered the spleen,heart,kidney meridians.The high-frequency major syndromes were low back pain and periumbilical pain,menstrual disorder,and most of them occurred during the menstrual period.The common dose was usually below 100 g,which mostly exceeded the dosage prescribed by Chinese pharmacopoeia."Wuzhuyu-Guizhi-Danggui"were the core compatibility combination.The key signaling pathways obtained from enrichment analysis mainly included the PI3K-Akt signaling pathway,AGE-RAGE signaling pathway,and endocrine resistance signaling pathway,among others.The key targets obtained from PPI network analysis included AKT1,STAT3,ESR1,among others.Conclusion:The compatibility pairs of Wuzhuyu were mainly composed of tonic herbs,which were primarily indicated for TCM gynecological disorders such as irregular menstruation and periumbilical pain.The therapeutic method was dominated by tonification,while the administration methods and processing approaches were designed with the primary goal of reducing toxicity.There may be a synergistic and toxicity-reducing effect in the compatibility of Wuzhuyu with Danggui,Renshen(Radix Ginseng),Ganjiang(Rhizoma Zingiberis)and other herbs.This study may provide evidence for the safe and rational clinical application of Wuzhuyu in gynecology,and may offer valuable insights into promoting the upgrade of its pharmacopoeia quality standards as well as the research on herb compatibility and prescriptions based on efficacy-toxicity correlation evaluation.
王艺;李双双;张天泽;杨菁华;郭威;王亮
青岛大学附属山东省妇幼保健院,山东 济南,250014山东省第一荣军优抚医院,山东 济南,250014北京中医药大学东直门医院,北京,100700青岛大学附属山东省妇幼保健院,山东 济南,250014青岛大学附属山东省妇幼保健院,山东 济南,250014青岛大学附属山东省妇幼保健院,山东 济南,250014
医药卫生
吴茱萸方剂中医妇科用药规律
WuzhuyuPrescriptionTCM gynecologyPrescription regularity
《中医临床研究》 2026 (5)
131-141,11
全国中药特色技术传承人才培训项目(国中医药人教函[2023]96号)中国妇幼研究会母胎医学专项(2023CAMCHS003A08)山东省泰山学者青年专家项目(tsqn202211360)山东省中医药重点学科(内分泌病学)——山东省妇幼保健院山东省重大科技创新工程(2017CXGC1308)山东省妇幼保健专项基金(YJKY2022-027,YJKY2022-021).
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