高明利教授治疗类风湿关节炎用药规律总结及机制分析

Analysis of Herb Use Rules and Mechanism in the Treatment of Rheumatoid Arthritis by Professor GAO Mingli

目的通过对门诊处方的收集整理,分析高明利教授治疗类风湿关节炎的用药规律、核心药物及作用机制。方法收集2021年7月—2022年12月,类风湿关节炎患者首次就诊于辽宁中医药大学附属医院,高明利教授专家门诊的首诊处方,采用数据挖掘联合网络药理学及分子对接的方法,运用《中医传承计算平台》对药物的频次、性味、归经和功效进行分类统计,对所有处方进行K-means聚类分析;运用R语言进行Apriori关联规则分析得到核心药物;通过TCMSP数据库查找核心药物活性成分及靶点,并在DisGeNet数据库中预测治疗靶点;对预测的治疗靶点进行GO、KEGG富集分析,构建治疗靶点的蛋白互作网络并进行重要治疗靶点的筛选;以重要治疗靶点作为蛋白受体,核心药物活性成分作为配体进行分子对接验证。结果研究共纳入中药处方169首,涉及中药216味,高频用药为穿山龙、甘草、延胡索、白芍、桂枝、川芎、黄芪、透骨草等;药物四气以温性为主,兼有寒性等;五味以甘味为主,兼有苦味等;归经以足厥阴肝经为首;功效以补虚为主,兼活血化瘀、清热、祛风湿等;聚类分析得到以穿山龙、延胡索、透骨草、川芎、桂枝为首的处方3类;关联规则分析根据置信度、支持度、提升度筛选出核心药物为透骨草、延胡索、穿山龙;药物有效活性成分有槲皮素、山柰酚等,药物预测治疗靶点118个;主要富集在TNF、IL17、HIF-1等炎性信号通路上;核心治疗靶点为TNF、IL6、IL1B、CCL2、IL10等。结论高明利教授门诊治疗类风湿关节炎的治疗原则以“通痹扶正”为主,以镇痛通络、益气扶正为主要的治疗方法,核心药物为穿山龙、延胡索、透骨草,其中有效成分为槲皮素、山柰酚等,能够作用于以TNF、IL6、IL1B、CCL2、IL10等为代表的治疗靶点通过TNF、IL-17等炎性信号通路发挥治疗效果。

Objective Through the collection of outpatient prescriptions,the author analyzed the medication rules,core herbs and mechanism of Professor GAO Mingli in the treatment of rheumatoid arthritis(RA).Methods The prescriptions of Professor GAO Mingli from the affiliated hospital of Liaoning university of traditional Chinese medicine for the treatment of RA from July 2021 to December 2022 were collected. The method of data mining,network pharmacology and molecular docking was adopted. The herbfrequency,properties,flavors,meridian and efficacy were classified and counted by the TCM InheritanceComputing Platform. K-means cluster analysis was performed for all prescriptions. The core herbs wereobtained by analyzing the association rules of Apriori using R language. Core herbs active ingredients andtargets were searched by TCMSP database,and therapeutic targets were predicted by DisGeNet database.GO and KEGG enrichment analysis were performed on the predicted therapeutic targets,protein interactionnetworks were constructed and important therapeutic targets were screened. Those targets were usedas protein receptors and core herbs active ingredients as ligands for 3D molecular docking verification.Results A total of 169 prescriptions were included in the study,involving 216 herbs. The high-frequencyherbs were Chuanshanlong(Dioscoreae Nipponicae Rhizoma),Gancao(Glycyrrhizae Radix Et Rhizoma),Yanhusuo(Corydalis Rhizoma),Baishao(Paeoniae Radix Alba),Guizhi(Cinnamomi Ramulus),Chuanxiong(Chuanxiong Rhizoma),Huangqi(Astragali Radix),Tougucao(Phryma Leptostachya),etc.The four properties of herbs were mainly warm. The five flavors were mainly sweet. The liver meridian wasthe first. The main effect was tonifying deficiency,promoting blood circulation and removing blood stasis,clearing heat,dispelling wind and dampness,etc. By cluster analysis,three kinds of prescriptions wereobtained,including Chuanshanlong(Dioscoreae Nipponicae Rhizoma),Yanhusuo(Corydalis Rhizoma),Tougucao(Phryma Leptostachya),Chuanxiong(Chuanxiong Rhizoma),Guizhi(Cinnamomi Ramulus).According to the degree of confidence,support and lift,the core herbs were screened out as Tougucao(Phryma Leptostachya),Yanhusuo(Corydalis Rhizoma),Chuanshanlong(Dioscoreae NipponicaeRhizoma). There were 118 predicted therapeutic targets,including quercetin and kaempferol. It was mainlyconcentrated in TNF,IL-17,HIF-1 and other inflammatory signaling pathways. The core therapeutictargets were TNF,IL6,IL1B,CCL2,IL10,etc. Conclusion Professor GAO Mingli's outpatient treatment ofRA is based on the principle of“Tongbi and Fuzheng”,which means the main treatment methods are clearout pain or numbness and strengthening the body resistance. The core herbs are Chuanshanlong(DioscoreaeNipponicae Rhizoma),Yanhusuo(Corydalis Rhizoma),Tougucao(Phryma Leptostachya),among whichthe effective ingredients are quercetin and kaempferol. It can act on therapeutic targets represented by TNF,IL6,IL1B,CCL2,IL10,etc.,and exert therapeutic effects through inflammatory signaling pathways such asTNF and IL-17.