异甘草素治疗高尿酸血症的潜在作用机制  

Potential mechanism of isoliquiritigenin in treatment of hyperuricemia

作　　者：杨静依 周红燕 袁晓庆 兰先明 孙福东[2] 赵泉[2] 张加余 YANG Jingyi;ZHOU Hongyan;YUAN Xiaoqing;LAN Xianming;SUN Fudong;ZHAO Quan;ZHANG Jiayu(School of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,P.R.China;Department of Pharmacy,Yantai Yuhuangding Hospital,Yantai 264000,Shandong,P.R.China;School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250300,Shandong,P.R.China)

机构地区：[1]滨州医学院药学院,山东烟台264003 [2]烟台毓璜顶医院药学部,山东烟台264000 [3]山东中医药大学药学院,山东济南250300

出　　处：《滨州医学院学报》2025年第1期50-57,共8页Journal of Binzhou Medical University

基　　金：山东省泰山学者青年专家项目(tsqn202103110);山东省中医药科技计划项目重点课题(Z-2022085);烟台市校地融合发展课题(20165701);烟台市省级以上领军人才配套支持项目(10073801)。

摘　　要：目的基于网络药理学、分子对接及体外实验探究异甘草素治疗高尿酸血症(hyperuricemia,HUA)的潜在作用机制。方法通过PubChem、Gencard等数据分析平台筛选异甘草素治疗HUA的潜在分子靶点,借助Cytoscape 3.7.1及STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)并筛选核心靶点。利用Metscape将异甘草素治疗HUA的潜在分子靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(KEGG)富集分析,并构建“靶点-通路”可视化网络。选取PPI网络排名靠前的HUA相关靶点与异甘草素进行分子对接验证,并用HK-2细胞进行MTT、实时定量PCR和免疫荧光等实验。结果最终筛选得到异甘草素治疗HUA排名前10位的潜在分子靶点包括CXCR4、BCL2L1、ALDH2、MCL、ABCG2等。GO和KEGG富集分析显示,异甘草素治疗HUA的潜在靶点主要调控ABC转运蛋白、P53等信号通路,影响ABC型转运蛋白活性、细胞对氮化合物的反应、调节炎症反应等病理过程。分子对接结果显示,异甘草素与CXCR4和ABCG2结合较稳定,与ALDH2虽然有很好的结合性能,但结合不稳定。细胞实验结果显示,异甘草素能够恢复HUA细胞模型的存活率,同时改善NO和ROS水平。异甘草素能够改善高尿酸对HK-2细胞CXCR4蛋白表达和mRNA表达的影响。结论异甘草素对高尿酸环境下的HK-2细胞具有保护作用,可有效地降低高尿酸环境对HK-2细胞造成的损伤。Objective To explore the potential mechanism of action of isoliquiritigenin for the treatment of hyperuricemia through network pharmacology,molecular docking,and in vitro experiments.Methods The potential molecular targets of isoliquiritigenin in the treatment of hyperuricemia were screened through data analysis platforms such as PubChem and Gencard.Protein-protein interaction(PPI)was constructed and core targets were screened by using Cytoscape 3.7.1 and STRING database.The potential molecular targets of isoliquiritigenin in the treatment of hyperuricemia were enriched by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)by using Metscape,and a"arget-pathway"visualization network was constructed.the HUA-related targets ranked high in PPI network were selected for molecular docking verification and HK-2cell were used for MTT,real-time quantitative PCR and immunofluorescence experiments.Results The top 10 potential molecular targets of isoliquiritigenin for anti-hyperuricemia were screened,including CXCR4,BCL2L1,ALDH2,MCL,ABCG2,etc.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the potential target of isoliquiritigenin for anti-Hyperuricemia was mainly to regulate ABC transporters,P53 and other signalling pathways affecting ABC transporters,cell response to nitrogen compounds,and regulate inflammation and other pathological processes.Molecular docking results showed that isoliquiritigenin was stable in binding with CXCR4 and ABCG2,but unstable in binding with ALDH2 although it had good binding properties.The results of cell experiments showed that isoliquiritigenin restored the survival rate of hyperuricemia cell models while improving the levels of NO and ROS.Isogliquiritin could improve the effects of high uric acid on CXCR4 protein expression and mRNA expression in HK-2 cells.Conclusion Isoliquiritigenin has a protective effect on HK-2 cells under high uric acid conditions and can effectively reduce the damage caused to HK-2 cells by the high uric ac

关 键 词：异甘草素 高尿酸血症 CXCR4 HK-2细胞 网络药理学 

分 类 号：R285[医药卫生—中药学]