铁死亡基因在儿童川崎病中的生物信息学分析及中药预测研究  

Bioinformatics analysis of ferroptosis genes in children with Kawasaki disease and prediction of traditional Chinese medicine

作　　者：宋哲 劳慧敏[2] 王晓[2] 张葆青[2] SONG Zhe;LAO Hui-min;WANG Xiao;ZHANG Bao-qing(First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Department of Pediatrics,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China)

机构地区：[1]山东中医药大学第一临床医学院,济南250355 [2]山东中医药大学附属医院儿科,济南250011

出　　处：《中华中医药杂志》2023年第5期2286-2291,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.82174177)。

摘　　要：目的:从铁死亡角度探讨儿童川崎病(KD)的发病机制,进而预测潜在治疗中药。方法:整合KD基因芯片数据和铁死亡相关基因,使用R语言limma包筛选差异表达基因(DEGs)。通过DAVID数据库对DEGs进行富集分析。利用STRING数据库、Cytoscape软件进行蛋白互作网络的拓扑分析以获得关键基因,并绘制ROC曲线以评估关键基因对KD的诊断价值。基于CIBERSORT反卷积算法进行免疫浸润分析。最后,通过SymMap数据库预测可靶向铁死亡治疗KD的潜在中药。结果:共发现35个儿童KD铁死亡相关DEGs,其中关键致病基因9个。活化的CD4+记忆性T细胞、γδT细胞、单核细胞、M0型巨噬细胞和中性粒细胞为KD患儿外周血高度活化的免疫细胞。经SymMap数据库预测,连翘和广枣是通过抑制铁死亡治疗KD最具潜力的中药。结论:KD引起的异常基因表达可通过促进铁离子的胞内转运和脂质积累、抑制GSH/GPX4信号轴等途径诱发细胞铁死亡,而铁死亡又介导了KD血管内皮损伤、氧化应激、炎症反应和免疫浸润等关键病理过程。IL1B、TLR4、MAPK14、LCN2和ALOX5的异常高表达可作为儿童KD的新型诊断标志物。连翘和广枣对于KD的治疗具有很大的研究价值。Objective:To explore the pathological mechanisms of Kawasaki disease(KD)in children from the perspective of ferroptosis,and then to predict the potential traditional Chinese medicine(TCM).Methods:The microarray data of KD and ferroptosis related genes were integrated,and the differentially expressed genes(DEGs)were screened by limma package in R software.The DAVID database was used to conduct the pathway enrichment of DEGs.The STRING database and Cytoscape software were used to analyze the topology of protein interaction network to obtain key genes,and the ROC curves were drawn to evaluate the diagnostic value of key genes in KD.Immune infiltration analysis was performed based on CIBERSORT deconvolution algorithm.Finally,the SymMap database was used to predict the potential TCM.Results:A total of 35 ferroptosisrelated DEGs were found in children with KD,including 9 key pathogenic genes.The results of immune infiltration analysis showed that the activated CD4+memory T cells,γδT cells,monocytes,M0 type macrophages and neutrophils were significantly increased in children with KD.According to the prediction of SymMap database,Forsythia suspensa and Choerospondiatis fructus were the most potential Chinese medicinal materials for the treatment of KD by inhibiting ferroptosis.Conclusion:Abnormal gene expression induced by KD can promote ferroptosis by promoting intracellular iron transport and lipid accumulation and inhibiting GSH/GPX4 signal axis,while ferroptosis mediates key pathological processes such as vascular endothelial injury,oxidative stress,inflammatory reaction and immune infiltration in KD.The abnormally high expression of IL1B,TLR4,MAPK14,LCN2 and ALOX5 may be the new diagnostic marker of KD.Forsythia suspensa and Choerospondiatis fructus have great research values for the treatment of KD.

关 键 词：川崎病 铁死亡 生物信息学 连翘 广枣 

分 类 号：R725.4[医药卫生—儿科]