目的 采用超高效液相-四级杆-静电场轨道阱高分辨质谱（UPLC-Q-Exactive Orbitrap-MS）联合网络药理学及分子对接技术，探究三金片治疗间质性膀胱炎的物质基础和作用机制。方法 通过UPLC-Q-Exactive Orbitrap-MS采集数据，结合建立的数据库表征三金片化学成分，依据SwissADME数据库的类药性≥3个“Yes”的评判标准，筛选活性成分；通过中药系统药理学数据库与分析平台（TCMSP）、SwissTargetPrediction数据库查找活性成分靶点；通过基因数据库筛选间质性膀胱炎靶点。药物靶点与疾病靶点取交集，输入String数据库和Cytoscape 3.7.2软件构建蛋白质-蛋白质相互作用（PPI）网络，筛选出核心靶点。利用DAVID数据库对核心靶点进行基因本体（GO）功能注释和京都基因与基因组百科全书（KEGG）通路富集分析；通过分子对接实验验证活性成分与核心靶点的结合能力，并结合分子动力学模拟评估关键复合物的结合稳定性。结果 从三金片中鉴定出51种化学成分，筛选活性成分39个；活性成分靶点与间质性膀胱炎靶点交集165个；GO功能注释获得1 205条条目，KEGG通路富集分析得到190条相关信号通路，涵盖炎症调控、免疫应答等关键生物学过程。分子对接结果显示，木犀草素、异鼠李素、山柰酚、白藜芦醇及柚皮苷查尔酮等活性成分，与TNF、AKT1、IL6、TP53、INS等核心靶点蛋白均具有良好的结合活性；分子动力学模拟进一步验证，结合能最优的木犀草素-TNF复合物结合能为-184.22 kJ·mol^-1，表明二者结合具有高度稳定性。结论 初步阐明三金片通过“多成分、多靶点、多通路”的整合调节模式治疗间质性膀胱炎的特点，其核心活性成分可能通过调控炎症相关靶点及通路发挥作用，为后续三金片药效机制的深入研究及临床应用拓展提供参考。

Objective To explore the material basis and mechanism of action of Sanjin Tablets in the treatment of interstitial cystitis by using ultra-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） combined with network pharmacology and molecular docking technology. Methods Data were collected by UPLC-QExactive Orbitrap-MS and the chemical components of Sanjin Tablets were characterized based on the established database. Active components were screened according to the criterion of ≥ 3 “Yes” in drug-likeness from the SwissADME database. The target proteins of active components were identified through traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP） and SwissTargetPrediction databases, and the target proteins of interstitial cystitis were screened through the gene database. The intersection of drug targets and disease targets was input into the String database and Cytoscape 3.7.2 software to construct a protein-protein interaction（PPI） network and screen out core targets. The core targets were subjected to gene ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis using the DAVID database. Molecular docking experiments were conducted to verify the binding ability of active components to core targets, and molecular dynamics simulations were used to evaluate the binding stability of key complexes. Results Fifty-one chemical components were identified in Sanjin Tablets, and 39 active components were screened. There were 165 intersections between the target proteins of active components and those of interstitial cystitis. GO functional annotation yielded 1,205 entries, and KEGG pathway enrichment analysis identified 190 related signaling pathways, covering key biological processes such as inflammation regulation and immune response. Molecular docking results showed that active components such as luteolin, isorhamnetin, kaempferol, resveratrol, and naringenin chalcone had good binding activity with core target proteins such as TNF, AKT1, IL6, TP53, and INS. Molecular dynamics simulations further verified that the binding energy of the luteolin-TNF complex was-184.22 k J·mol^-1, indicating a highly stable binding. Conclusion This study initially clarified the characteristics of Sanjin Tablets in treating interstitial cystitis through an integrated regulation mode of “multiple components, multiple targets, and multiple pathways”. Its core active components may exert their effects by regulating inflammation-related targets and pathways, providing a reference for the in-depth study of the pharmacological mechanism and clinical application expansion of Sanjin Tablets.

R285.5

全国中药特色技术传承人才培训项目(国中医药人教函[2023]96号); 广西中医药大学研究生教育创新计划项目(YCSY2025093)