基于网络药理学和分子对接技术探讨四逆散治疗非酒精性脂肪性肝炎的潜在作用机制  

Potential Mechanism of Sini Powder(四逆散)in the Treatment of Non-alcoholic Steatohepatitis Based on Network Pharmacology and Molecular Docking

作　　者：李哲[1] 李娜[1] 赵蓝青青 于永洲 潘海峰[1] 熊辉 赵春颖[1] LI Zhe;LI Na;ZHAO Lanqingqing;YU Yongzhou;PAN Haifeng;XIONG Hui;ZHAO Chunying(Chengde Medical College,Chengde 067000,Heibei,China)

机构地区：[1]承德医学院,河北承德067000

出　　处：《辽宁中医药大学学报》2022年第8期99-105,F0003,共8页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金(82104384);河北省教育厅青年项目(QN2021008);中央引导地方科技发展资金项目(216Z2501G);承德医学院高层次人才科研启动基金(202103);河北省高校重点学科建设项目(冀教高[2013]4);河北省科技厅技术创新引导专项-科技工作会商;承德医学院本草基因组青年PI科技创新团队项目。

摘　　要：目的基于网络药理学与分子对接技术探讨四逆散治疗非酒精性脂肪性肝炎作用机制。方法通过TCMSP数据库筛选四逆散的活性成分及作用靶点。采用GeneCards数据库及OMIM数据库检索非酒精性脂肪性肝炎疾病相关靶点。利用R语言获得药物成分与疾病的交集基因,通过Cytoscape 3.7.1构建“药物-活性成分-靶点-疾病”关系网络图,将交集基因通过Bisogenet数据分析平台进行蛋白互作网络分析,并进行基因本体GO和KEGG通路富集分析。利用AutoDockTools 1.5.6和AutoDockVina 1.1.2软件中完成分子对接。结果四逆散的主要活性成分241个、对应靶点318个,药物疾病共同靶点57个;GO富集分析得1307个条目(P<0.05),KEGG通路富集分析筛选出122条信号通路(P<0.05),主要涉及非酒精性脂肪性肝病、脂质和动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、肿瘤坏死因子等信号通路。分子对接结果显示山柰酚、槲皮素、异鼠李素与MAPK8有较强的结合能力。结论四逆散干预NASH具有多途径、多靶点作用特点,四逆散中的有效成分主要通过RELA、AKT1、MAPK8、IL-6、JUN等靶点调节多条信号通路发挥对NASH的治疗作用,为后续研究提供参考和依据。Objective To investigate the mechanism of Sini Powder(四逆散)in the treatment of nonalcoholic steatohepatitis based on online pharmacology and molecular docking techniques.Methods The active components and target of Sini Powder were screened by TCMSP database.GeneCards database and OMIM database were used to search the disease-related targets of nonalcoholic steatohepatitis.The intersection genes of drug components and disease were obtained by R language,and the relationship network map of“drug-active components-target-disease”was constructed by Cytoscape 3.7.1.The intersection genes were analyzed by Bisogenet data analysis platform for protein interaction network analysis,and the enrichment analysis of gene ontology GO and KEGG pathways was carried out.The molecular docking was completed in AutoDockTools 1.5.6 and AutoDockVina 1.1.2 software.Results There were 241 main active components,318 corresponding targets and 57 common drug disease targets in Sini Powder.GO enrichment analysis obtained 1307 entries(P<0.05),KEGG pathway enrichment analysis screened out 122 signaling pathways(P<0.05),mainly involving nonalcoholic fatty liver disease,lipid and atherosclerosis,age-RAGE signaling pathway in diabetic complications,tumor necrosis factor signaling pathway and other signaling pathways.The molecular docking results showed that kaempferol,quercetin and isorhamnetin had strong binding ability with MAPK8.Conclusion Sini Powder has the characteristics of multi-pathway and multi-target effects in the intervention of NASH.The effective components of Sini Powder mainly regulate multiple signaling pathways through RELA,AKT1,MAPK8,IL-6,JUN and other targets to play a therapeutic role in the treatment of NASH,which provides reference and basis for subsequent studies.

关 键 词：网络药理学 四逆散 非酒精性脂肪性肝炎 分子对接 作用机制 

分 类 号：R285.5[医药卫生—中药学]