基于生物信息学技术的中药治疗代谢相关脂肪性肝病的用药规律及其机制研究  

Medication rule and mechanism of traditional Chinese medicine in treating metabolism-associated fatty liver disease based on bioinformatics technology

作　　者：张云坤 姚蓉 李林 李文莉 李长青 潘宇[1,6] 李顺祥 ZHANG Yunkun;YAO Rong;LI Lin;LI Wenli;LI Changqing;PAN Yu;LI Shunxiang(School of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Institute of Bioengineering,Hunan Food and Drug Vocational College,Changsha,Hunan 410208,China;Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases,Changsha,Hunan 410208,China;Hunan Institute for Drug Control,Changsha,Hunan 410001,China;Changsha Yichu Pharmaceutical Technology Co.,Ltd.,Changsha,Hunan 410125,China;Guangxi Botanical Garden of Medicinal Plants,Nanning,Guangxi 530023,China)

机构地区：[1]湖南中医药大学药学院,中国湖南长沙410208 [2]湖南食品药品职业学院生物工程研究所,中国湖南长沙410208 [3]湖南省中美老年性退行性疾病治疗药物国际联合研究中心,中国湖南长沙410208 [4]湖南省药品检验检测研究院,中国湖南长沙410001 [5]长沙易初医药科技有限公司,中国湖南长沙410125 [6]广西壮族自治区药用植物园,中国广西南宁530023

出　　处：《Digital Chinese Medicine》2023年第3期257-271,共15页数字中医药（英文）

基　　金：Natural Science Foundation of Hunan Province(2021JJ80055);Natural Science Foundation of Guangxi Province(2020JJA140044);Funding Project for the Employment and Entrepreneurship of Overseas Students in Hunan Province[2022]。

摘　　要：目的分析中药治疗代谢相关脂肪性肝病(MAFLD)的主要证型、用药规律和核心处方特征,预测核心药方抗MAFLD作用机理,为中医药临床应用及新药研发提供参考。方法检索中国知网、维普、万方数据库自建库至2022年7月关于中医药治疗MAFLD的期刊文献;运用Excel 2019及中医传承计算平台(V3.0)对有效处方进行频数分析、关联规则分析及聚类分析,通过网络药理学方法预测核心药方抗MAFLD关键成分、靶点及作用通路;最后,通过分子对接技术对关键成分与核心靶点进行反向验证。结果共筛选出文献218篇,涉及方剂352首,中药270味,药物使用总频次3901次,共收集病例10915例,其中男性患病率更高;中医证型主要包括痰瘀互结证、肝郁脾虚证和肝胆湿热证,其中山楂、丹参、茯苓、泽泻、柴胡和白术使用频次最高;四气以寒、温为主;五味以苦、甘为主;主要归脾、肝经;功效以健脾补虚、利水渗湿、活血化瘀和清热为主。关联规则运算得到核心药对及组合20个,聚类分析获得核心药方3组。网络药理学研究表明,核心药方“山楂-丹参-泽泻-柴胡-茯苓”治疗MAFLD主要成分为槲皮素、芹菜素、葛根素、木犀草素、熊果酸、山柰酚、丹参酮IIA、大黄素、丹皮酚等,涉及丝氨酸/苏氨酸激酶1(AKT1)、肿瘤蛋白p53基因(TP53)、白细胞介素(IL)-6、IL-1β、信号转导及转录激活因子3(STAT3)、表皮生长因子受体(EGFR)、过氧化物酶体增殖物激活受体γ(PPARG)等关键靶点;分子对接实验显示其可能通过调节脂质与动脉粥样硬化、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-AKT)等信号通路相关靶点发挥作用。结论中医治疗MAFLD的原则以“疏肝健脾、化痰祛湿、清热利湿、活血化瘀”为主,核心药方可能通过多成分、多靶点、多条信号通路介导产生抗MAFLD效应。本研究为中医药治疗MAFLD临床用药提供了理论依据,为进一步�Objective To analyze the main syndrome types,medication rules,and core prescription characteristics of traditional Chinese medicine(TCM)in the treatment of metabolism-associated fatty liver disease(MAFLD),and to predict the anti-MAFLD mechanism of core formula,so as to provide references for the clinical application of TCM and the development of new drugs.Methods Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),and Wanfang Database since the establishment of the database to July 2022.Excel 2019 and Chinese Medicine Inheritance Computing Platform(V3.0)were used for frequency analysis,association rule analysis,and cluster analysis of effective prescriptions.The key components,targets,and action pathways of anti-MAFLD core formulas were predicted by network pharmacology.Finally,the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology.Results A total of 218 articles were screened and selected,including 352 prescriptions,involving 270 traditional Chinese herbs.The drugs were used a total of 3901 times,and a total of 10915 cases were collected,among which the prevalence rate was higher in males.The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome,liver depression and spleen deficiency syndrome,and damp-heat in liver and gallbladder syndrome,among which Shanzha(Crataegi Fructus),Danshen(Salviae Miltiorrhizae Radix et Rhizoma),Fuling(Poria),Zexie(Alismatis Rhizoma),Chaihu(Bupleuri Radix),and Baizhu(Atractylodis Macrocephalae Rhizoma)were the most frequently used.The properties of Chinese medicine primarily encompassed thermal characteristics,with a predominant emphasis on cold and warm;the flavors of herbs were predominantly characterized by bitterness and sweetness,while the majority exhibited tropism towards the spleen and liver meridians.The drugs were primarily classified based on their efficacy in t

关 键 词：代谢相关脂肪性肝病 生物信息学技术 用药规律 核心组方 作用机理 

分 类 号：R259[医药卫生—中西医结合] Q811.4[医药卫生—中医内科学]