目的 基于网络药理学和分子对接技术探讨胃复春片治疗慢性萎缩性胃炎（CAG）的作用机制，结合体外细胞实验初步验证胃炎相关靶点。方法 综合运用中药系统药理数据库与分析平台（TCMSP）、台湾中医药、DrugBank数据库和中药分子机制的生物分析工具检索胃复春片的活性成分和作用靶点，通过OMIM、GeneCards、DisGeNET数据库获取CAG的疾病靶点，取交集获得共同靶点。将作用靶点导入STRING在线平台构建蛋白质相互作用（PPI）网络，并进行拓扑分析筛选核心靶点。利用DAVID 6.8数据库进行基因本体论（GO）功能、京都基因和基因组百科全书（KEGG）通路富集分析。最后对主要活性成分与关键靶点进行分子对接，同时运用实时荧光定量PCR （qRT-PCR）检测CAG相关基因mRNA的表达。结果 经筛选获得胃复春片活性成分60个，作用靶点550个，经筛选获得胃复春片-CAG关键靶点30个。胃复春片作用靶点涉及磷脂酰肌醇-3激酶/蛋白激酶（PI3K-Akt）、肿瘤坏死因子（TNF）、核转录因子-κB （NF-κB）、胃癌相关通路等多条信号通路，通过调控细胞增殖、分化、凋亡、炎症反应等发挥抗CAG作用。分子对接结果表明，活性成分与核心靶点有良好的结合能力。细胞实验结果也证实，胃复春片可通过下调肿瘤坏死因子-α（TNF）、白细胞介素-6（IL6）、白细胞介素-1β（IL1B）、信号转导及转录激活蛋白-3（STAT3）的mRNA表达量（P<0.01），上调蛋白激酶（AKT1）、白细胞介素-4（IL4）的mRNA表达量治疗CAG。结论 胃复春片能够通过多成分-多靶点-多通路发挥治疗CAG的作用，其主要作用成分有槲皮素、β-豆甾醇、辛弗林、新橙皮苷、新北美圣草苷等，其主要靶点有TNF、IL6、IL1B、STAT3、AKT1、IL4等。

Objective To explore the mechanism of Weifuchun Tablets in treating chronic atrophic gastritis (CAG) based on network pharmacology combined with molecular docking, and to preliminarily verify the related targets by in vitro cellular test. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Database@Taiwan, DrugBank database and BATMAN-TCM were used to screen and predict the active compounds and targets of Weifuchun Tablets. Targets of CAG were collected by OMIM, GeneCards and DisGeNET databases, and common targets are obtained by intersection. STRING online platform was used to conduct protein interaction analysis on the target sites, and protein interaction (PPI) network was constructed and the core target was found. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed by DAVID 6.8 database. Finally, the main active ingredients and key targets were molecularly docked, while real-time fluorescence quantitative PCR (qRT-PCR) was used to verify the CAG related genes mRNA expression. Results 60 active components and 550 targets of Weifuchun Tablets were screened, and 30 key targets were obtained by topological analysis. The targets of Weifuchun Tablets involved PI3K-Akt, TNF, NF-κB and gastric cancer related signaling pathways, which played an anti-CAG effect by regulating cell proliferation, differentiation, apoptosis and inflammatory response. The results of molecular docking showed that active ingredients had good binding ability to the core target. The results of in vitro cell test also confirmed that Weifuchun Tablets could down-regulate the mRNA expressions of tumor necrosis factor-α (TNF), interleukin-6 (IL6), interleukin-1β (IL1B) and signal transducer and activator of transcription-3 (STAT3) (P < 0.01), upregulate the mRNA expression levels of protein kinase (AKT1) and interleukin-4 (IL4) to treat CAG. Conclusion Weifuchun Tablets can play a role in the treatment of CAG through "multi-component, multi-target and multi-pathway". Its main active ingredients are quercetin, β-stigmasterol, synephrine, neohesperidin, neokaempferoside, etc. The main targets are TNF, IL6, IL1B, STAT3, AKT1, IL4, etc.

R285.5

北京市双一流高层次人才科研经费资助项目（1000041510053）；基于中西医一体化的胃肠动力功能智能检测评估系统与多模态经络调控机制研究（2021-JYB-YGJH001）