摘要
目的通过生物信息学从铁死亡角度探讨溃疡性结肠炎(ulcerative colitis,UC)活动期和缓解期的异同发病机制,并筛选可能干预UC的天然药物,为UC的治疗开辟新途径。方法在GEO数据库中检索与UC相关并符合筛选条件的数据集,进行limma差异分析,分别获得UC活动期、UC缓解期的差异表达靶点。在FerrDb平台收集与铁死亡相关的靶点。构建铁死亡与UC差异表达共同靶点的蛋白互作(protein-protein interaction network,PPI)网络。通过R软件对与铁死亡相关的UC活动期和缓解期的靶点分别进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。利用CMap平台筛选干预不同时期UC的天然活性成分,并通过TCMSP找到天然活性成分所来源的中药。结果GEO数据库筛选出GSE53306、GSE38713、GSE11223数据集,从UC活动期和缓解期样本分别筛选出差异表达靶点3985个和659个。将收集得到的388个铁死亡相关靶点分别与UC不同时期相关靶点取交集,导入STRING数据库,得到与铁死亡相关的UC靶点间的PPI,筛选到10个核心基因。富集分析显示,UC活动期与刺激的反应相关性较高,UC缓解期与细胞解毒的反应、过氧化物的代谢相关性较高。神经退行性疾病-多种疾病是UC活动期与缓解期的共同信号通路。CMap平台筛选结果显示,大豆苷元、芦丁、胡椒碱、白藜芦醇、杨梅素、苦参碱、槲皮素、黄体酮、染料木素、大黄素为最有可能治疗UC的天然活性成分,且这些活性成分广泛来源于多种中药,分子对接结果显示天然活性成分与其对应的靶点结合能均<5.0 kcal/mol。结论IL-6、IL-1β、CD44是与UC最相关的靶点,可通过神经退行性疾病、脂质和动脉粥样硬化等信号通路影响UC病情严重程度。大豆苷元、芦丁、胡椒碱等10种天然活性成分可能成为治疗UC的关键药物,为UC的临床治疗开辟新途径�
Objective To investigate the similarities and differences in the pathogenesis of ulcerative colitis(UC)from the perspective of ferroptosis through bioinformatics,and to screen natural drugs that may interfere with UC,so as to open up new avenues for the treatment of UC.Methods The data sets related to UC that met the screening criteria were retrieved from GEO database,limma differential analysis was performed,and the differential expression targets of UC in active and remission stage were obtained.Targets associated with ferroptosis were collected in the FerrDb platform.The protein-protein interaction network(PPI)of common targets of ferroptosis and UC differential expression were constructed.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were performed by R software for the targets associated with ferroptosis in active and remission stages of UC,respectively.The CMap platform was used to locate the natural active ingredient for intervening different targets of UC and to find the traditional Chinese medicine(TCM)from which the natural active ingredients were derived by TCMSP.Results The GSE53306,GSE38713 and GSE11223 data sets were retrieved through the GEO database,and 3985 and 659 differential expression targets were obtained from UC active and remission stage samples,respectively.A total of 388 ferroptosis-associated targets were intersected with UC targets at different stages.The PPI networks between ferroptosis related targets and UC related targets was obtained by importing the STRING database,and 10 core genes were screened.GO and KEGG enrichment analysis showed that the response to stimulation was highly correlated during the active stage of UC,and the response to cellular detoxification and metabolism of peroxides were relatively advanced during the remission stage of UC.Neurodegenerative diseases-multiple diseases were common signaling pathways between UC active and remitting stages.CMap platform screening results showed that daidzein,rutin,piperine,resveratrol,myr
作者
龚卓之
曹增
姚梦茜
孙梓宽
王倩影
刘涛
GONG Zhuo-zhi;CAO Zeng;YAO Meng-xi;SUN Zi-kuan;WANG Qian-ying;LIU Tao(Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China;Graduate School of Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中草药》
CAS
CSCD
北大核心
2023年第7期2187-2196,共10页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金项目(81830115)。
