世界中西医结合杂志2025，Vol.20Issue(10)：1965-1977,13.DOI:10.13935/j.cnki.sjzx.251007
基于生物信息学分析动脉粥样硬化铜死亡相关基因及调控中药预测
Bioinformatics Analysis of Cuproptosis-Related Genes and Screening of Chinese Medicines for Prevention and Treatment in Atherosclerosis
摘要
Abstract
Objective To investigate the expression and potential mechanisms of cuproptosis-related genes in atherosclerosis(AS)based on bioinformatics analysis,and to screen Chinese medicines capable of regulating these genes.Methods Key differentially expressed genes(DEGs)associated with cuproptosis were identified from the GSE100927 dataset,and their correlations were analyzed.The dataset samples were subjected to clustering analysis,and gene set varia-tion analysis(GSVA)was applied to examine pathway enrichment across subtypes.Predictive models were constructed using multiple machine learning algorithms,and the results were correlated with cuproptosis-related DEGs to identify key genes.Potential Chinese medicines for AS prevention and treatment were subsequently screened.Results A total of 12 cuproptosis-related DEGs were identified,including NOD-like receptor thermal protein domain associated protein 3(NLRP3),ATPase copper transporting α(ATP7A),and Solute carrier family 31 copper transporter 1(SLC31A1),which exhibited strong syn-ergistic or antagonistic relationships.Based on the expression of cuproptosis-related DEGs,AS patients could be divided into two molecular subtypes,showing distinct gene expression patterns.GSVA revealed pathway enrichment mainly in the NLR signaling pathway,ErbB signaling pathway,and Hedgehog signaling pathway.Machine learning models predicted coiled-coil domain containing 2-like(C2CD2L),nucleoporin 62(NUP62),nucleosome assembly protein 1-like 5(NAP1L5),Zinc finger E-box-binding homeobox 1(ZEB1),and Rho GTPase activating protein 27(ARHGAP27)as AS signature genes.Based on cuproptosis-related DEGs and AS signature genes,Chinese medicine prediction analysis indica-ted that the identified herbs were mainly cold,warm,or neutral in nature;predominantly bitter and sweet in flavor;and pri-marily entered the liver,kidney,spleen,stomach,and heart meridians.Their functions were mostly related to clearing heat and removing toxins,promoting blood circulation and removing stasis,tonifying deficiency and strengthening the body,and inducing diuresis to drain dampness.Common high-frequency herbs included Asteriscus Pseudosciaenae,Colla Carassii,and Ginseng Radix et Rhizoma.Conclusion Cuproptosis plays an important role in the occurrence,progression,and diag-nosis of AS.The mutual regulatory effects among 12 cuproptosis-related DEGs,including SLC31A1 and lipoic acid syn-thetase(LIAS),and their involvement in the Hedgehog and NLR signaling pathways may represent key mechanisms under-lying cuproptosis-related AS pathogenesis.Among them,NLRP3,SLC31A1,ferredoxin 1(FDX1),lipoyltransferase 1(LIPT2),cyclin dependent kinase inhibitor 2A(CDKN2A),glutaminase(GLS),and glycine cleavage system H protein(GCSH)are identified as key cuproptosis-related genes,while C2CD2L,NUP62,NAP1L5,ZEB1,and ARHGAP27 are AS signature genes.Chinese medicines such as Asteriscus Pseudosciaenae,Colla Carassii,and Ginseng Radix et Rhizoma may serve as potential molecular sources for AS prevention and treatment.关键词
动脉粥样硬化/铜死亡相关基因/生物信息学/免疫浸润/中药预测Key words
Atherosclerosis/Cuproptosis-related Genes/Bioinformatics/Immune Infiltration/Chinese Medicine Prediction分类
医药卫生引用本文复制引用
贾思涵,连妍洁,尚菊菊,刘红旭,周琦,来晓磊..基于生物信息学分析动脉粥样硬化铜死亡相关基因及调控中药预测[J].世界中西医结合杂志,2025,20(10):1965-1977,13.基金项目
2022年度北京中医药"十四五"重点专科心血管科(BJZKLCO011) （BJZKLCO011）
北京市重大疑难疾病中西医协同攻关项目(2023BJSZDYNJBXTGG-011) （2023BJSZDYNJBXTGG-011）
首都医科大学附属北京中医医院科技发展基金资助项目(LYYB202303) （LYYB202303）
