摘要
背景:基底膜基因与类风湿关节炎的发生发展密切相关,但不同中医证型下基底膜相关基因在其发病机制中的作用尚不明确。目的:基底膜基因联合转录组学分析探讨类风湿关节炎5种不同中医证型的发病机制差异,并进行潜在治疗药物预测。方法:基于GEO数据库整理类风湿关节炎相关中医证型芯片数据以及基底膜相关基因,利用R-limma包筛选差异表达基因,Mfuzz包进行表达趋势分析。借助STRING数据库构建PPI网络,UPset筛选关键基因,通过R-clusterProfiler包对差异表达基因进行GSEA及富集分析,同时绘制ROC曲线评估基底膜相关核心靶点对5种证型分别的诊断价值。基于CIBERSORT核心算法计算每种证型的免疫浸润情况。最后,利用SymMap和COREMINE数据库预测可靶向基底膜相关核心基因治疗类风湿关节炎不同证型的潜在中药及小分子药物。结果与结论:①在5种类风湿关节炎中医证型中(风湿痹阻证、寒湿痹阻证、肝肾亏虚证、气血两虚证及血瘀阻络证)分别筛选出67,47,59,57,55个基底膜相关差异表达基因,其中关键靶点分别为5,7,5,3,5个。③各证型中富集最多的为细胞基质黏附、免疫细胞迁移及胶原代谢等生物过程以及细胞外基质受体相互作用、PI3K-Akt、局灶性粘连和Rap1信号通路等。④药物预测结果显示,土茯苓、川乌、绵马贯众及黄精是通过影响基底膜基因治疗5种类风湿关节炎中医证型最具潜力的中药。⑤结果证实,基底膜相关基因的异常表达可能是通过调控细胞附着、免疫细胞迁移及炎症反应等多个途径影响类风湿关节炎的发生和发展,在不同证型中有着差异表现,其中ITGA6可作为5种类风湿关节炎证型中共同的诊断标志物。清热解毒类中药可能是类风湿关节炎不同证型治疗中可以贯穿始终的潜在有效药物。
BACKGROUND:Basement membrane genes are closely related to the occurrence and development of rheumatoid arthritis,but the role of basement membrane-related genes in the pathogenesis of rheumatoid arthritis under different traditional Chinese medicine patterns is not yet clear.OBJECTIVE:To explore the differences in the pathogenesis of rheumatoid arthritis with five different traditional Chinese medicine syndromes based on the analysis of basement membrane-related genes and transcriptomics,and to predict potential therapeutic drugs.METHODS:Rheumatoid arthritis-related traditional Chinese medicine syndrome microarray data and basement membrane-related genes were collected from the GEO database.The differentially expressed genes were screened using the R-limma package,and the expression trends were analyzed using the Mfuzz package.The protein-protein interaction network was constructed using the STRING database and key genes were selected using UPset.The differentially expressed genes were subjected to gene set enrichment analysis(GSEA)and enrichment analysis using the R-clusterProfiler package.Receiver operating characteristics curves were plotted to evaluate the diagnostic value of core basement membrane-related targets for each of the five syndromes.The immune infiltration of each syndrome was calculated using the CIBERSORT algorithm.Finally,potential traditional Chinese medicines and small molecule drugs targeting core basement membrane-related genes for the treatment of different traditional Chinese medicine syndromes of rheumatoid arthritis were predicted using SymMap and COREMINE databases.RESULTS AND CONCLUSION:(1)67,47,59,57,and 55 basement membrane-related differentially expressed genes were screened for the five traditional Chinese medicine syndromes of rheumatoid arthritis(obstruction syndrome,cold-dampness obstruction syndrome,liver-kidney deficiency syndrome,qiblood deficiency syndrome,and blood stasis obstructing collaterals syndrome),with 5,7,5,3,and 5 key targets identified,respectively.(2)The most e
作者
刘源
渠源
万雅坤
郭婧宇
姜萍
Liu Yuan;Qu Yuan;Wan Yakun;Guo Jingyu;Jiang Ping(First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;College of Rehabilitation,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;Affiliated Hospital,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2025年第25期5486-5500,共15页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(82274481,81874449),项目负责人:姜萍
国家中医药管理局科技司共建科技项目(GZY-KJS-SD-2023-041),项目负责人:姜萍
山东省自然科学基金项目(ZR2022LZY004),项目负责人:姜萍
齐鲁张氏风湿骨病中医药特色技术项目(鲁卫函[2022]93号),项目负责人:姜萍。
关键词
基底膜相关基因
证型
类风湿关节炎
中药
转录组学分析
GSEA分析
免疫浸润
分子对接
药物预测
机制研究
basement membrane-related gene
phenotype
rheumatoid arthritis
traditional Chinese medicine
transcriptomics analysis
GSEA analysis
immune infiltration
molecular docking
drug prediction
mechanism study
