南方医科大学学报2024，Vol.44Issue(7)：1243-1255,13.DOI:10.12122/j.issn.1673-4254.2024.07.04
鬼箭羽通过调节EGFR酪氨酸激酶抑制剂耐药信号通路延缓糖尿病肾病的进展
Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway
摘要
Abstract
Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.关键词
鬼箭羽/糖尿病肾病/GEO数据库/网络药理学/分子对接/信号通路/动物实验Key words
euonymus alatus/diabetic kidney disease/GEO database/network pharmacology/molecular docking/signaling pathways/animal experiments引用本文复制引用
王瑾瑾,崔文飞,窦雪伟,尹冰磊,牛钰琪,牛羚,闫国立..鬼箭羽通过调节EGFR酪氨酸激酶抑制剂耐药信号通路延缓糖尿病肾病的进展[J].南方医科大学学报,2024,44(7):1243-1255,13.基金项目
国家自然科学基金(82104748) （82104748）
河南省科技攻关计划项目(242102311282) Supported by National Natural Science Foundation of China(82104748). （242102311282）
