目的 通過網(wǎng)絡(luò)藥理學方法和分子對接技術(shù)對鐵皮石斛治療慢性萎縮性胃炎的潛在作用機制進行探討。方法 基于CNKI和PubMed數(shù)據(jù)庫篩選出鐵皮石斛的有效成分,通過Swiss Target Prediction數(shù)據(jù)庫對活性成分靶點進行預測,運用Cytoscape軟件構(gòu)建"有效成分-靶點"網(wǎng)絡(luò)。通過GeneCards和OMIM數(shù)據(jù)庫收集疾病靶點并與藥物靶點相交集,得出鐵皮石斛治療慢性萎縮性胃炎的有效靶點。通過STRING數(shù)據(jù)庫進行蛋白互相作用(PPI)分析、Metascape數(shù)據(jù)庫進行基因本體(GO)分析和京都基因與基因組百科全書(KEGG)通路分析、AutoDockVina軟件進行分子對接驗證。結(jié)果 通過篩選得出鐵皮石斛的有效成分有14種,靶點188個,疾病靶點有768個。鐵皮石斛治療慢性萎縮性胃炎的有效靶點為38個。PPI分析得出鐵皮石斛作用于AKT1、EGFR、MAPK3、PTGS2、MMP-9、SRC、HSP90AA1等核心靶點對慢性萎縮性胃炎發(fā)揮作用。GO分析及KEGG通路分析篩選出細胞外基質(zhì)、蛋白激酶活性、對氧化應激的反應等生物學功能和IL-17、癌癥的途徑、細胞凋亡、鈣信號等10條通路與之密切相關(guān)。分子對接結(jié)果驗證了有效成分和關(guān)鍵靶點的相互作用,其中柚皮素、槲皮素與核心靶點MMP-9的對接親和度較高。結(jié)論 通過網(wǎng)絡(luò)藥理學證明了鐵皮石斛主要通過多靶點、多通路和多途徑對慢性萎縮性胃炎發(fā)揮其治療作用,為治療慢性萎縮性胃炎提供新的方向和依據(jù)。

Objective The potential mechanism of Dendrobium officinale in treatment of chronic atrophic gastritis was discussed by network pharmacological methods and molecular docking technology.Methods The active components of Dendrobium officinale were screened based on CNKI and PubMed databases, and their targets were predicted through Swiss Target Prediction database. The “active component-target” network was constructed by Cytoscape software. Disease targets were collected through GeneCards and OMIM databases, and intersected with drug targets to obtain the effective targets of Dendrobium officinale in treatment of chronic atrophic gastritis. PPI analysis was carried out through String database, GO analysis and KEGG pathway analysis were carried out through Metascape database, and molecular docking verification was carried out by AutoDockVina software.Results The results showed that there were 14 effective components, 188 targets, and 768 disease targets of Dendrobium officinale, and 38 effective targets of Dendrobium officinale in treatment of chronic atrophic gastritis. PPI analysis showed that Dendrobium officinale acted on AKT1, EGFR, MAPK3, PTGS2, MMP-9, SRC, HSP90AA1 and other core targets, and played a role in chronic atrophic gastritis. GO analysis and KEGG pathway analysis showed that the biological functions such as extracellular matrix, protein kinase activity, and response to oxidative stress were closely related to IL-17, cancer pathway, apoptosis, and calcium signal. The molecular docking results verified the interaction between the active ingredient and the core target. The docking affinity between naringin, quercetin and the core target MMP-9 was the highest.Conclusion Through the scientific nature of network pharmacology, this study proved that Dendrobium officinale mainly plays its therapeutic role in chronic atrophic gastritis through multi-target, multi-channel and multi-channel, and provides a new direction and basis for the treatment of chronic atrophic gastritis.

R286.5

國家自然科學基金資助項目(81560773);貴州農(nóng)村產(chǎn)業(yè)革命石斛專項資金(黔石科合[2020]004號);貴州省高層次創(chuàng)新型人才項目(黔科合平臺人才[2020]6016)