小柴胡汤治疗肝炎时出现肝损伤的“效-毒”作用网络分析与机制预测  

Network analysis and mechanism prediction of “effectiveness-toxicity” of liver injury in treatment of hepatitis with Xiaochaihu Decoction

作　　者：刘静 李晓宇[2] 吴恺怿[2] 黄娜娜 孙蓉 LIU Jing;LI Xiao-yu;WU Kai-yi;HUANG Na-na;SUN Rong(The Second Hospital of Shandong University,Jinan 250033,China;Institute of Advanced Medical Sciences,Shandong University,Jinan 250012,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东大学第二医院,山东济南250033 [2]山东中医药大学,山东济南250012 [3]山东大学高等医学研究院,山东济南250355

出　　处：《中草药》2019年第21期5135-5144,共10页Chinese Traditional and Herbal Drugs

基　　金：山东省重点研发计划(重大关键技术)项目(2016ZDJS07A21);山东省重点研发计划项目(2017CXGC1301);国家自然科学基金面上项目(81773997);国家重点基础研究发展计划(“973”)中医基础理论专项(2009CB522802);泰山学者工程专项经费项目(ts201511107)

摘　　要：目的运用网络药理学研究模式,基于小柴胡汤治疗肝炎过程中造成药物性肝损的临床不良反应伤(ADR)信息挖掘,探讨小柴胡汤治疗肝炎时产生肝损伤的"效-毒"作用靶点、通路和机制。方法以小柴胡汤为研究对象,借助整合药理学平台构建"效-毒"作用网络,预测分析其关键靶点和通路,应用Cytoscape软件对关键靶标所参与的通路整理分析,得到"效-毒"共同参与的通路及作用机制。结果小柴胡汤治疗肝炎时产生肝损伤的"效-毒"作用分析得出,在度值排名前100的候选靶标中共同靶标有HADHA、HADH、NSDHL、ADH1A、ALDH3A2、GCK等40个,小柴胡汤中共同参与"效-毒"作用的化学成分包括柴胡27个、人参74个、半夏13个、生姜8个、甘草32个、大枣39个、黄芩33个,共226个成分,共同作用于内分泌系统、神经系统、雌激素信号通路、趋化因子信号通路、内分泌和代谢疾病、非酒精性脂肪肝病(NAFLD)、神经退行性疾病7条通路参与"效-毒"过程。结论小柴胡汤治疗肝炎时产生肝损伤的"效-毒"作用可能与Ras/Raf/MEK/ERK、NF-κB、PI3K/AKT信号传导途径密切相关,通过调控细胞增殖、细胞凋亡、调控炎症因子的表达发挥作用。Objective To explore the"efficacy-toxicity"targets,pathways,and mechanism of Xiaochaihu Decoction in the treatment of hepatitis based on the ADR information excavating of drug-induced liver injury in the treatment of hepatitis with Xiaochaihu Decoction.Methods Taking Xiaochaihu Decoction as the research object,the integrated pharmacology platform was used to analyze and predict key targets and pathways.Cytoscape software was used to collate and analyze key targets and pathways to obtain co-participation pathways and mechanisms of"efficacy-toxicity".Results The analysis of the effect of Xiaochaihu Decoction for liver injury in the treatment of hepatitis showed that there were 40 common targets such as HADHA,HADH,NSDHL,ADH1 A,ALDH3 A2,and GCK among the top 100 candidate targets with degree value.The chemical components jointly participated in the network of"effect-toxicity"which belonged to Xiaochaihu Decoction including 27 components in Bupleuri Radix,74 components in Ginseng Radix,13 components in Pinelliae Rhizoma,8 components in Zingiberis Rhizoma,32 components in Glycyrrhizae Radix et Rhizoma,39 components in Jujubae Fructus,and 33 components in Scutellaria baicalensis.A total of 226 components were involved in the"effect-toxicity"process through endocrine and metabolic diseases,non-alcoholic fatty liver disease(NAFLD),estrogen signaling pathway,neurodegenerative diseases,nervous system,chemokine signaling pathway,and endocrine system.Conclusion The"efficacy-toxicity"effect of Xiaochaihu Decoction on liver injury in the treatment of hepatitis may be closely related to Ras/Raf/MEK/ERK,NF-B,and PI3 K/AKT signal transduction pathway.It plays a role by regulating cell proliferation,cell apoptosis and the expression of inflammatory factors,which provides a theoretical basis for further pharmacological and toxicological verification and chemical separation research.It plays a role by regulating cell proliferation,cell apoptosis and the expression of inflammatory factors.

关 键 词：小柴胡汤 肝炎 药物性肝损伤 网络药理学 “效-毒”作用 

分 类 号：R285.5[医药卫生—中药学]