目的 運用網(wǎng)絡(luò)藥理學(xué)研究芍藥甘草湯治療乙型病毒性肝炎所致肝損傷的作用機制。方法 通過中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）獲取芍藥甘草湯的化合物及靶點，以口服生物利用度（OB）≥30%和類藥（DL）≥0.18為閾值進行化合物篩選，將靶點輸入Uniprot獲取靶點對應(yīng)的基因Symbol；從TTD、OMIM等數(shù)據(jù)庫獲取乙型病毒性肝炎的相關(guān)靶點并篩選出與芍藥甘草湯靶點基因的交集基因；運用Cytoscape3.8.0軟件繪制活性成分-靶點、疾病-中藥-化合物-交集靶點（基因）網(wǎng)絡(luò)圖；運用String構(gòu)建蛋白相互作用網(wǎng)絡(luò)，再用R語言的Bioconductor安裝包，進行GO富集及KEGG通路富集分析，并聯(lián)合主要化合物、交集基因與通路分析結(jié)果，繪制成分-靶點-通路網(wǎng)絡(luò)圖；用Vina軟件對篩選出來的結(jié)果進行分子對接。結(jié)果 篩選得到芍藥甘草湯有效成分105種、有效成分靶點214個；篩選得到乙型病毒性肝炎疾病靶點5 984個，藥物-疾病交集基因198個；經(jīng)蛋白互作網(wǎng)絡(luò)及拓?fù)浣Y(jié)構(gòu)分析得到21個核心靶點，121條相互作用關(guān)系；槲皮素、山柰酚、柚皮素等為芍藥甘草湯的主要活性成分，PPARA、RB1、TP53、MAPK3、AKT1、STAT3、JUN等為主要作用靶點。GO富集分析顯示靶點所在的細(xì)胞組分主要為薄膜筏、膜微域、膜區(qū)域；生物學(xué)過程主要富集在有對金屬離子的響應(yīng)、對脂多糖的反應(yīng)；分子功能主要為核受體活性、轉(zhuǎn)錄因子活性。KEGG富集發(fā)現(xiàn)膜區(qū)由糖基化終末產(chǎn)物介導(dǎo)的AGE-RAGE通路、乙型肝炎通路等為主要通路。進一步篩選核心靶點及化合物成分進行分子對接顯示MAPK3、AKT1、STAT3、JUN作為核心靶點可與槲皮素、山柰酚、柚皮素穩(wěn)定對接。結(jié)論 通過網(wǎng)絡(luò)藥理學(xué)及分子對接的方法，找到了芍藥甘草湯治療慢性乙型病毒性肝炎肝損傷可能的潛在靶點，預(yù)測了其發(fā)揮藥理作用的關(guān)鍵通路。

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

國家中醫(yī)藥管理局全國名老中醫(yī)藥專家盛國光傳承工作室項目建設(shè)（國中醫(yī)藥人教函［2018-134號）；國家中醫(yī)臨床研究基地業(yè)務(wù)建設(shè)科研專項課題（JDZX2012051）