目的 運用網(wǎng)絡(luò)藥理學(xué)和分子對接探討澳洲茄邊堿治療鼻咽癌的潛在作用靶點以及可能存在的作用機制。方法 通過BATMAN、CTD、Genecards、HERB、Swiss Target Prediciton、TCMSP及Pharm Mapper數(shù)據(jù)庫獲取澳洲茄邊堿潛在作用靶點，利用Drugbank、GeneCards、MalaCards、OMIM及OpenTarget數(shù)據(jù)庫篩選鼻咽癌相關(guān)靶點，應(yīng)用R語言軟件篩選藥物與疾病共同靶點，應(yīng)用STRING_v12.0數(shù)據(jù)庫、Cytoscape v3.10.0軟件構(gòu)建澳洲茄邊堿–鼻咽癌共同靶點的蛋白相互作用（PPI）網(wǎng)絡(luò)；基于R4.4.3軟件用clusterProfiler包對澳洲茄邊堿–鼻咽癌共同靶點進(jìn)行基因本體（GO）功能和京都基因與基因組百科全書（KEGG）通路富集分析；最后，利用CytoNCA、MCODE插件及CytoHubba擴展程序計算節(jié)點得分，獲得核心靶點，并通過AutoDockTools_1.5.7軟件進(jìn)行分子對接驗證。結(jié)果 網(wǎng)絡(luò)藥理學(xué)分析得到澳洲茄邊堿–鼻咽癌共同靶點121個，獲得蛋白激酶B1（Akt1）、白蛋白（ALB）、膜聯(lián)蛋白A5（ANXA5）、B細(xì)胞淋巴瘤2（Bcl2）、BCL2樣1（Bcl2L1）、胱天蛋白酶-3（CASP3）、胱天蛋白酶-9（CASP9）、基質(zhì)金屬蛋白酶9（MMP9）、信號轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子3（STAT3）等29個核心靶點；GO顯示澳洲茄邊堿潛在靶點涉及最顯著的生物過程（BP）為對脂多糖的反應(yīng)和對細(xì)菌分子的反應(yīng)，分子功能（MF）包括內(nèi)肽酶活性、羧酸結(jié)合和蛋白絲氨酸/蘇氨酸激酶活性，細(xì)胞組分（CC）是富纖維蛋白-1顆粒、細(xì)胞膜脂質(zhì)筏和細(xì)胞膜微區(qū)等；KEGG通路分析涉及腫瘤壞死因子（TNF）信號通路、絲裂原激活的蛋白激酶（MAPK）信號通路、白細(xì)胞介素-17（IL-17）信號通路、p53信號通路等；分子對接結(jié)果顯示，澳洲茄邊堿與核心靶點均具有較好的結(jié)合能力。結(jié)論 澳洲茄邊堿可能通過與Akt1、ALB等多靶點結(jié)合及調(diào)控TNF、MAPK等多信號通路來參與鼻咽癌免疫調(diào)控、細(xì)胞凋亡與存活，進(jìn)而發(fā)揮抗鼻咽癌作用。

Objective To investigate the potential therapeutic targets and mechanisms of solamargine in the treatment of nasopharyngeal carcinoma based on network pharmacology and molecular docking. Methods Potential targets of solamargine were collected from BATMAN, CTD, GeneCards, HERB, SwissTargetPrediction, TCMSP, and PharmMapper databases. NPC-related targets were retrieved from DrugBank, GeneCards, MalaCards, OMIM, and OpenTarget databases. Common targets between solamargine and NPC were identified using R software. A protein-protein interaction (PPI) network was constructed with STRING_v12.0 database and Cytoscape v3.10.0. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using clusterProfiler packages in Rv4.4.3. Finally, core targets were identified by calculating node scores using the CytoNCA and MCODE plugins, along with the CytoHubba extension, followed by molecular docking validation performed with AutoDockTools_ 1.5.7 software. Results Common targets (121) of solamargine-nasopharyngeal carcinoma were obtained by network pharmacology analysis. There are 29 core targets such as Akt1, ALB, ANXA5, Bcl2, Bcl2L1, CASP3, CASP9, MMP9, STAT3 were identified. GO showed that the most significant BP involved in the potential targets of solamargine were response to lipopolysaccharide and response to molecule of bacterial origin, MF included endopeptidase activity, carboxylic acid binding and protein serine/threonine kinase activity, CC were ficolin-1-rich granule, membrane raft and membrane microdomain. KEGG pathway analysis involved TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and p53 signaling pathway, etc. The molecular docking results demonstrated that solamargine had the ability to bind to the core target. Conclusion Solamargine may participate in the immune regulation, apoptosis and survival of nasopharyngeal carcinoma by binding to multiple targets such as Akt1 and ALB and regulating multiple signaling pathways such as TNF and MAPK, thereby exerting an anti-nasopharyngeal carcinoma effect.

R285

北京醫(yī)學(xué)獎勵基金會課題研究項目（YXJL-2024-1324-0383）；廣西藥學(xué)會醫(yī)院藥學(xué)科研項目（GXYXH1-202206）