目的 运用网络药理学研究芍药甘草汤治疗乙型病毒性肝炎所致肝损伤的作用机制。方法 通过中药系统药理学数据库与分析平台（TCMSP）获取芍药甘草汤的化合物及靶点，以口服生物利用度（OB）≥30%和类药（DL）≥0.18为阈值进行化合物筛选，将靶点输入Uniprot获取靶点对应的基因Symbol；从TTD、OMIM等数据库获取乙型病毒性肝炎的相关靶点并筛选出与芍药甘草汤靶点基因的交集基因；运用Cytoscape3.8.0软件绘制活性成分-靶点、疾病-中药-化合物-交集靶点（基因）网络图；运用String构建蛋白相互作用网络，再用R语言的Bioconductor安装包，进行GO富集及KEGG通路富集分析，并联合主要化合物、交集基因与通路分析结果，绘制成分-靶点-通路网络图；用Vina软件对筛选出来的结果进行分子对接。结果 筛选得到芍药甘草汤有效成分105种、有效成分靶点214个；筛选得到乙型病毒性肝炎疾病靶点5 984个，药物-疾病交集基因198个；经蛋白互作网络及拓扑结构分析得到21个核心靶点，121条相互作用关系；槲皮素、山柰酚、柚皮素等为芍药甘草汤的主要活性成分，PPARA、RB1、TP53、MAPK3、AKT1、STAT3、JUN等为主要作用靶点。GO富集分析显示靶点所在的细胞组分主要为薄膜筏、膜微域、膜区域；生物学过程主要富集在有对金属离子的响应、对脂多糖的反应；分子功能主要为核受体活性、转录因子活性。KEGG富集发现膜区由糖基化终末产物介导的AGE-RAGE通路、乙型肝炎通路等为主要通路。进一步筛选核心靶点及化合物成分进行分子对接显示MAPK3、AKT1、STAT3、JUN作为核心靶点可与槲皮素、山柰酚、柚皮素稳定对接。结论 通过网络药理学及分子对接的方法，找到了芍药甘草汤治疗慢性乙型病毒性肝炎肝损伤可能的潜在靶点，预测了其发挥药理作用的关键通路。

Objective Using network pharmacology to study the mechanism of Shaoyao Gancao Decoction in the treatment of liver injury caused by chronic viral hepatitis B. Methods Compound and target of Shaoyao Gancao Decoction were obtained through systematic pharmacology database and analysis platform of Traditional Chinese medicine (TCMSP). Compound screening was conducted with the threshold of oral bioavailability (OB) ≥ 30% and class drug (DL) ≥ 0.18. Target was input into Uniprot to obtain gene Symbol corresponding to target.Targets related to HEPATITIS B were obtained from TTD, OMIM, GeneCards, DrugBank and PharmGkb data database, and intersection genes with target genes of Shaoyao Gancao Decoction were screened out. Cytoscape3.8.0 software was used to draw the network map of active ingredient-target, disease-Chinese medicine-compound-intersection target (gene). The protein interaction network was constructed by using String. The GO enrichment and KEGG pathway enrichment analysis was carried out in the R language Bioconductor installation package. The component-target-pathway network diagram was drawn by combining the main compounds, intersection genes and pathway analysis results. Vina software was used to perform molecular docking on the screened results. Results There were 105 kinds of effective components and 214 targets of active components in Shaoyao Gancao Decoction. Five thousand nine hundred and eighty-four targets of chronic viral hepatitis B and 198 drug-disease intersection genes were selected.After the network interaction network and topology structure analysis, 21 core targets and 121 interaction relationships are obtained. Quercetin, kaempferol and naringenin are the main active components of Shaoyao Gancao Decoction, while PPARA, RB1, TP53, MAPK3, AKT1, STAT3 and JUN are the main targets. GO enrichment analysis showed that the target cells were grouped into membrane rafts, membrane microdomains, and membrane regions. Biological processes are mainly concentrated in response to metal ions and reaction to lipopolysaccharides. The main molecular functions are nuclear receptor activity and transcription factor activity. KEGG enrichment showed that age-RAGE pathway and hepatitis B pathway mediated by glycosylated end products were the main pathways in the membrane area. Further screening of core targets and compound components for molecular docking showed that MAPK3, AKT1, STAT3 and JUN were core targets for stable docking with small molecules of quercetin, kaempferol and naringenin. Conclusion Through network pharmacology and molecular docking, this study found the potential target of Shaoyao Gancao Decoction for the treatment of liver injury in chronic viral hepatitis B, and predicted the key pathway of its pharmacological effect. It provides new ideas and methods for the development of classical prescription and the clinical application of related drugs.

R285.5

国家中医药管理局全国名老中医药专家盛国光传承工作室项目建设（国中医药人教函［2018-134号）；国家中医临床研究基地业务建设科研专项课题（JDZX2012051）