目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)探討胃復(fù)春片治療慢性萎縮性胃炎（CAG）的作用機(jī)制，結(jié)合體外細(xì)胞實(shí)驗(yàn)初步驗(yàn)證胃炎相關(guān)靶點(diǎn)。方法 綜合運(yùn)用中藥系統(tǒng)藥理數(shù)據(jù)庫與分析平臺(tái)（TCMSP）、臺(tái)灣中醫(yī)藥、DrugBank數(shù)據(jù)庫和中藥分子機(jī)制的生物分析工具檢索胃復(fù)春片的活性成分和作用靶點(diǎn)，通過OMIM、GeneCards、DisGeNET數(shù)據(jù)庫獲取CAG的疾病靶點(diǎn)，取交集獲得共同靶點(diǎn)。將作用靶點(diǎn)導(dǎo)入STRING在線平臺(tái)構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，并進(jìn)行拓?fù)浞治龊Y選核心靶點(diǎn)。利用DAVID 6.8數(shù)據(jù)庫進(jìn)行基因本體論（GO）功能、京都基因和基因組百科全書（KEGG）通路富集分析。最后對(duì)主要活性成分與關(guān)鍵靶點(diǎn)進(jìn)行分子對(duì)接，同時(shí)運(yùn)用實(shí)時(shí)熒光定量PCR （qRT-PCR）檢測(cè)CAG相關(guān)基因mRNA的表達(dá)。結(jié)果 經(jīng)篩選獲得胃復(fù)春片活性成分60個(gè)，作用靶點(diǎn)550個(gè)，經(jīng)篩選獲得胃復(fù)春片-CAG關(guān)鍵靶點(diǎn)30個(gè)。胃復(fù)春片作用靶點(diǎn)涉及磷脂酰肌醇-3激酶/蛋白激酶（PI3K-Akt）、腫瘤壞死因子（TNF）、核轉(zhuǎn)錄因子-κB （NF-κB）、胃癌相關(guān)通路等多條信號(hào)通路，通過調(diào)控細(xì)胞增殖、分化、凋亡、炎癥反應(yīng)等發(fā)揮抗CAG作用。分子對(duì)接結(jié)果表明，活性成分與核心靶點(diǎn)有良好的結(jié)合能力。細(xì)胞實(shí)驗(yàn)結(jié)果也證實(shí)，胃復(fù)春片可通過下調(diào)腫瘤壞死因子-α（TNF）、白細(xì)胞介素-6（IL6）、白細(xì)胞介素-1β（IL1B）、信號(hào)轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄激活蛋白-3（STAT3）的mRNA表達(dá)量（P<0.01），上調(diào)蛋白激酶（AKT1）、白細(xì)胞介素-4（IL4）的mRNA表達(dá)量治療CAG。結(jié)論 胃復(fù)春片能夠通過多成分-多靶點(diǎn)-多通路發(fā)揮治療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，其主要靶點(diǎn)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

北京市雙一流高層次人才科研經(jīng)費(fèi)資助項(xiàng)目（1000041510053）；基于中西醫(yī)一體化的胃腸動(dòng)力功能智能檢測(cè)評(píng)估系統(tǒng)與多模態(tài)經(jīng)絡(luò)調(diào)控機(jī)制研究（2021-JYB-YGJH001）