基于网络药理学探讨大补脾汤治疗肝癌的作用机制  

Study on the Mechanism of Dabupi Decoction in the Treatment of Liver Cancer Based on Network Pharmacology

作　　者：骆亚莉 安方玉 颜春鲁 冯彩琴 刘永琦 李研 王碧雯 Luo Yali;An Fangyu;Yan Chunlu;Feng Caiqin;Liu Yongqi;Li Yan;Wang Biwen(Gansu University of Chinese Medicine,Key Laboratory for Excavation,Innovation and Transformation of Traditional Chinese Medicine in Gansu Province,Lanzhou 730000,China;Gansu University of Chinese Medicine,Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education,Lanzhou 730000,China;The Second Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学甘肃省中医方药挖掘与创新转化重点实验室,兰州730000 [2]甘肃中医药大学敦煌医学与转化教育部重点实验室,兰州730000 [3]甘肃中医药大学第二附属医院,兰州730000

出　　处：《世界科学技术-中医药现代化》2021年第6期1792-1802,共11页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：敦煌医学与转化省部共建教育部重点实验室开放基金(DHYX17-12):敦煌方大补脾汤联合环磷酰胺对H22实体瘤鼠模型肿瘤生长的影响作用研究;负责人:骆亚莉;甘肃省中医方药挖掘与创新转化重点实验室开放基金(ZYFY-2019-006):基于网络药理学的黄芪抗炎、抗肿瘤机制及其物质基础研究,负责人:骆亚莉。

摘　　要：目的利用网络药理学的方法,建立大补脾汤的活性成分-作用靶点-通路的网络图,对作用靶点的基因功能和通路进行富集分析,从而探讨大补脾汤治疗肝癌的可能作用机制。方法通过TCMSP数据库、中国台湾中医药资料库获得大补脾汤主要活性成分。采用Swiss Target Prediction预测活性成分的潜在靶点,并与肝癌疾病靶点数据进行比对,获得大补脾汤治疗肝癌的作用靶点。采用DAVID数据库平台对作用靶点的GO注释和KEGG通路进行富集分析和蛋白功能归属。最后通过Cytoscape构建大补脾汤治疗肝癌的"活性成分-作用靶点-通路"网络图。结果大补脾汤潜在的有效成分共有118个,其中人参、甘草、旋覆花含有65种成分可能具有治疗肝癌的作用。大补脾汤治疗肝癌的可能靶点共29个,其中EGFR、SRC、PTGS2、MMP9、MMP2、MCL1、MET、AR和ESR1等可能为关键靶点基因,涉及到对微小RNAs、雌激素受体通路、肿瘤相关通路等的调控作用。结论大补脾汤中山奈酚、槲皮素、木犀草素等可能通过调控微小RNAs和雌激素信号通路等机制,作用于EGFR、ESR1、SRC、MET等靶点发挥治疗肝癌的作用,为大补脾汤药效机制的多角度研究和肝癌的中医药治疗提供思路。Objective Using the method of network pharmacology,author explored the possible mechanism of Dabupi Decoction in the treatment of liver cancer.Methods The main active components of Dabupi Decoction were obtained from TCMSP database and Taiwan(China) Traditional Chinese medicine database.SWISS-target prediction was used to predict the potential target of the active ingredients,and compared with the target data of liver cancer disease to obtain the target of Dabupi Decoction in the treatment of liver cancer.GO annotation and KEGG pathway were enriched and analyzed by David database platform.Finally,the network diagram of active component-target-pathway of Dabupi Decoction in the treatment of liver cancer was constructed by Cytoscape.Results There were 118 potential active ingredients in Dabupi Decoction,among which there were 65 ingredients in Radix Ginseng,Radix Glycyrrhizae and Flos Inulae which may have therapeutic effect on liver cancer.Also,we predicted 29 possible target genes in the treatment of liver cancer with Dabupi Decoction,and EGFR,SRC,PTGS2,MMP9,MMP2,MCL1,MET,AR and ESR1 may be the key target genes,which were involved in the regulation of microRNAs,Estrogen signaling pathway and tumor-related pathway.Conclusion Kaempferol,Quercetin and Luteolin in Dabupi Decoction may act on EGFR,ESR1,SRC,MET and other targets in the treatment of liver cancer through the regulation of microRNAs and Estrogen signaling pathways.This study provides an idea for the multi-angle study of the pharmacodynamic mechanism of Dabupi Decoction and the treatment of liver cancer with traditional Chinese medicine.

关 键 词：大补脾汤 肝癌 网络药理学 作用机制 

分 类 号：R289.5[医药卫生—方剂学]