目的 基于網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接方法探討三七治療胃癌前病變機(jī)制。方法 通過(guò)中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫(kù)與分析平臺(tái)（TCMSP）篩選三七有效成分和靶點(diǎn)，通過(guò)Uniprot數(shù)據(jù)庫(kù)將獲取的蛋白靶點(diǎn)轉(zhuǎn)換為人類基因靶點(diǎn)，通過(guò)SwissTarget Prediction數(shù)據(jù)庫(kù)進(jìn)行成分潛在靶點(diǎn)預(yù)測(cè)補(bǔ)充。通過(guò)GeneCards數(shù)據(jù)庫(kù)篩選胃癌前病變疾病相關(guān)靶點(diǎn)。篩選出三七治療胃癌前病變交集靶點(diǎn)利用STRING數(shù)據(jù)庫(kù)與Cytoscape 3.9.1軟件構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)。利用David數(shù)據(jù)庫(kù)進(jìn)行基因本體論（GO）和京都基因與基因組百科全書（KEGG）通路富集分析；運(yùn)用AutoDock vina對(duì)三七有效成分（配體）與核心靶點(diǎn)（受體）進(jìn)行分子對(duì)接，利用PyMOL軟件將結(jié)果進(jìn)行可視化處理。結(jié)果 共收集到三七8種有效成分及三七治療胃癌前病變的交集靶點(diǎn)128個(gè)；三七治療胃癌前病變的5個(gè)最核心靶點(diǎn)分別為信號(hào)轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄激活蛋白3（STAT3）、絲裂原活化蛋白激酶1（MAPK1）、腫瘤蛋白P53（TP53）、蛋白激酶B（Akt1）、90KDA熱休克蛋白ΑA1重組蛋白（HSP90AA1），2個(gè)核心有效活性成分為槲皮素和人參皂苷F₂。GO富集分析顯示，相關(guān)靶點(diǎn)參與基因調(diào)控、細(xì)胞凋亡、DNA及RNA轉(zhuǎn)錄等多個(gè)生物學(xué)過(guò)程發(fā)揮作用。KEGG富集分析顯示，三七治療胃癌前病變?cè)诎┌Y通路富集最明顯，核心靶點(diǎn)還參與了包括Janus激酶-信號(hào)轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄激活因子（JAK/STAT）、MAPK、TP53、磷脂肌醇3-激酶/蛋白激酶B（PI3K/Akt）信號(hào)通路在內(nèi)的多種信號(hào)通路途徑發(fā)揮作用。結(jié)論 三七治療胃癌前病變具有多成分、多靶點(diǎn)、多通路的特點(diǎn)，機(jī)制復(fù)雜，可能主要通過(guò)癌癥通路途徑發(fā)揮作用。

Objective To explore the mechanism of Notoginseng Radix et Rhizoma for the treatment of gastric precancerous lesions based on network pharmacology and molecular docking methods. Methods To screen Notoginseng Radix et Rhizoma active ingredients and targets by TCMSP, the protein targets obtained were converted into human gene targets through the Uniprot database, and the potential targets of ingredients were predicted and supplemented through the SwissTargetPrediction database. To screen the gastric precancerous lesions disease-related targets through Genecards database. The protein interaction (PPI) network was constructed using STRING database and Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using David database. AutoDock vina was used to molecularly dock the active ingredients (ligands) of NotoginsengRadix et Rhizoma with the core targets (receptors). Results A total of 8 effective components of Notoginseng Radix et Rhizoma and 128 intersectional targets of Panax notoginseng in treatment of gastric precancerous lesions were collected. The five core targets of Notoginseng Radix et Rhizoma in treatment of gastric precancerous lesions were signal transduction and transcription-activating protein 3 (STAT3), mitogen activated protein kinase 1 (MAPK1), tumor protein P53 (TP53), protein kinase B (Akt1), and 90KDA heat shock protein ΑA1 recombinant protein (HSP90AA1). The two core active ingredients were quercetin and ginsenoside F₂. GO enrichment analysis showed that related targets played a role in many biological processes, such as gene regulation, cell apoptosis, DNA and RNA transcription. KEGG enrichment analysis showed that Notoginseng Radix et Rhizoma had the most obvious enrichment in the cancer pathway in treatment of gastric prelesions. Core targets are also involved in various signaling pathways, including the Janus kinase-signal transduction and transcriptional activator (JAK/STAT), MAPK, TP53, and phospholipinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Conclusion NotoginsengRadix et Rhizoma has the characteristics of multi-component, multi-target and multi-pathway in the treatment of gastric precancerous lesions, and its mechanism is complex, which may play its role mainly through the cancer pathway.

R285.5

國(guó)家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2017YFC1700601）；武漢市醫(yī)學(xué)科研項(xiàng)目（WZ20A07）；武漢市中醫(yī)藥科研項(xiàng)目（WZ22Q28）