基于网络药理学探讨扶正祛瘀药对治疗子宫平滑肌肉瘤的作用机制  

The Mechanism of Fuzheng Quyu Formula(扶正祛瘀药对)in Treatment of Uterine Leiomyosarcoma Based on Network Pharmacology Study

作　　者：杨璇 李冬华[1] 任慧 罗文婷 陈宗舜 YANG Xuan;LI Donghua;REN Hui;LUO Wenting;CHEN Zongshun(School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学中医药学院,北京100069

出　　处：《中医药导报》2024年第4期35-43,共9页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(81774072);北京市自然科学基金资助项目(7202015)。

摘　　要：目的:运用网络药理学研究扶正祛瘀药对——黄芪-党参-三棱-莪术治疗子宫平滑肌肉瘤(uLMS)的作用机制,以期为uLMS的治疗和研究提供思路。方法:在TCMSP数据库中检索药物有效成分及作用靶点,基于GeneCards、OMIM、PharmGkb、DrugBank数据库收集疾病相关靶点,取两者靶点交集得到扶正祛瘀药对治疗uLMS的作用靶点。运用Cytoscape软件构建“化合物-靶点”网络,在STRING平台构建蛋白互作网络,并使用Cytoscape软件对蛋白互作网络进行拓扑分析得到核心基因。运用R语言对交集靶点进行GO和KEGG通路富集分析。使用Autodock Vina软件将核心基因与活性成分进行分子对接验证。采用CCK-8实验、TUNEL、流式细胞术以及实时荧光定量PCR实验,对网络药理学预测结果进行验证。结果:网络药理学筛选出扶正祛瘀药对治疗uLMS的有效成分35个,包括槲皮素、山柰酚、木犀草素等。作用于疾病的靶点为110个,拓扑分析得到12个核心基因,涉及TP53、AKT1、JUN、MYC等。GO富集分析共涉及生物过程2 162条,细胞组分42个,分子功能152条。KEGG富集分析筛选得到165条与u LMS相关通路。扶正祛瘀药对可能通过细胞凋亡、氧化反应、脂多糖应答等生物学过程治疗uLMS,涉及脂质与动脉粥样硬化、PI3K-AKT等信号通路。分子对接核心靶点与配体化合物能够展现出较好的亲和力。体外实验结果表明扶正祛瘀药对能降低uLMS细胞活力,促进uLMS细胞凋亡,抑制uLMS细胞中AKT1 mRNA、TP53 mRNA表达。结论:扶正祛瘀药对可以通过抑制uLMS细胞的活力、促进凋亡来发挥抗uLMS作用,其机制与TP53、AKT1等核心靶点有关。Objective:To investigate the therapeutic mechanism of Fuzheng Quyu Formula of Huangqi(Astragalus mongholicus),Dangshen(Codonopsis pilosula),Sanleng(Rhizoma spargani)and Ezhu(Curcuma zedoaria)on uterine leiomyosarcoma(uLMS)using network pharmacology in order to provide insights for its treatment and research.Methods:Effective components and corresponding targets were retrieved from TCMSP database.The disease-related targets were collected from GeneCards,OMIM,PharmGkb,and DrugBank databases.The intersection between these two sets of targets was obtained as the putative targets for the Fuzheng Quyu Formula on uLMS.A"compound-target"network was constructed using Cytoscape software.Protein-protein interaction(PPI)network was built with STRING platform and analyzed by Cytoscape software for topology analysis to obtain core genes.GO and KEGG pathway enrichment analyses of the intersecting targets were performed with R language.Molecular docking validation of core genes and active ingredients was conducted using Autodock Vina sofware.Results of network pharmacology prediction were verified by CCK-8 assay,TUNEL,flow cytometry,and real-time fluorescence quantitative PCR experiments.Results:Network pharmacology screening identified 35 effective components from Fuzheng Quyu Formula,including quercetin,kaempferol,luteolin,etc.These components targeted at 110 disease-relevant targets,which resulted in 12 core genes,including TP53,AKT1,JUN,MYC,etc.GO enrichment analysis covered 2162 biological processes,42 cellular components,and 152 molecular functions.KEGG enrichment analysis revealed 165 pathways related to uLMS.Fuzheng Quyu Formula may affect cell apoptosis,oxidation reaction,lipopolysaccharide response,etc.,involving lipid metabolism and atherosclerosis signaling pathways such as PI3K-AKT.Core targets and their ligand compounds showed good affinity through molecular docking.In vitro experimental results suggested that Fuzheng Quyu Formula could reduce the viability of uLMS cells,promote their apoptosis,and inhibit the expr

关 键 词：子宫平滑肌肉瘤 扶正祛瘀药对 网络药理学 细胞增殖 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]