整合生物信息学探究骨质疏松症和类风湿性关节炎潜在关键共同生物标志物及其靶向治疗中药活性成分筛选  

Integration of bioinformatics to explore potential key common biomarkers of osteoporosis and rheumatoid arthritis and screening of traditional Chinese medicine active ingredients for targeted therapy

作　　者：冯艳花 张竞竞[2] 王绍辉 FENG Yanhua;ZHANG Jingjing;WANG Shaohui(Henan No.3 Provincial People′s Hospital,Zhengzhou 450000,China;Medical College,Qingdao Binhai University,Affiliated Hospital of Qingdao Binhai University,Qingdao 266555,China;School of Ethnic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]河南省直第三人民医院,河南郑州450000 [2]青岛滨海学院医学院,青岛滨海学院附属医院<青岛军民融合医院>,山东青岛266555 [3]成都中医药大学民族医药学院,四川成都611137

出　　处：《药学研究》2023年第2期82-88,共7页Journal of Pharmaceutical Research

基　　金：国家自然科学基金青年基金(No.82104534);山东省高等学校青创人才引育计划资助(No.2019-81);青岛市科技惠民示范引导专项(No.20-3-4-52-nsh)。

摘　　要：目的利用生物信息学探讨骨质疏松症(OP)和类风湿性关节炎(RA)的关系并进一步挖掘其潜在靶向治疗中药活性成分。方法从GEO数据库下载基因芯片GSE56116和GSE93776,利用GEO2R在线分析工具分别筛选骨质疏松症和类风湿性关节炎的差异基因,进一步从GeneCards数据库下载骨质疏松症和类风湿性关节炎相关靶点,将两个数据库获得的结果合并去重后构建PPI互作网络图;用Cytoscape软件(3.7.2版本)中的插件MCODE和Cytohubba识别关键Cluster和Hub基因,然后用R软件(3.6.3版本)进行GO富集和KEGG通路分析,最后利用CTD数据库筛选靶向Hub基因的中药活性成分。结果通过GEO数据库分别获得骨质疏松症和类风湿性关节炎差异基因815个和22个,从GeneCards数据库分别获得骨质疏松症和类风湿性关节炎相关靶点4463个和1135个,合并去重后分别得到骨质疏松症相关靶点4968个,类风湿性关节炎相关靶点1144个,两者映射出673交集靶点;以degree≥10为条件筛选获得10个Hub基因STAT3、MAPK1等;GO分析获得骨质疏松症和类风湿性关节炎相关生物学过程(BP)964条,细胞成分(BP)34条,分子功能(MF)50条;KEGG通路富集获得144条;进一步筛选出白藜芦醇、槲皮素、姜黄素等28个可能靶向调控骨质疏松症和类风湿性关节炎的中药活性成分。结论骨质疏松症和类风湿性关节炎的发生发展涉及众多靶点和通路,其中,STAT3、MAPK1等10个Hub基因与骨质疏松症和类风湿性关节炎有着密切的联系,这些共有靶点可能是通过白细胞介素-17(IL-17)、Toll样受体、Th17细胞分化、T细胞受体、缺氧诱导因子1(HIF-1)、丝裂原活化蛋白酶(MAPK)、破骨细胞分化等通路从而调控骨质疏松症和类风湿性关节炎的发生发展,挖掘出28个潜在中药活性成分,这为进一步深入揭示骨质疏松症和类风湿性关节炎的共同调控机制和靶向调控药物的发现提供依据。Objective To investigate the relationship between osteoporosis(OP)and rheumatoid arthritis(RA)by using bioinformatics analysis and further explore the potential targeted therapeutic Chinese medicine active ingredients.Methods Gene chip GSE56116 and GSE93776 were downloaded from GEO database,and the differential genes of OP and RA were screened by GEO2R online analysis tool.OP and RA related targets were downloaded from GeneCards database,and then the results obtained from the two databases were combined and de-duplicated,as well as the PPI interaction network diagram was constructed.The key Cluster and Hub genes were identified by MCODE and Cytohubba plug-ins in Cytoscape software(version:3.7.2).Then,the GO enrichment and KEGG pathway analysis were performed by R software(version:3.6.3).Finally,CTD database was used to screen the active ingredients of TCM targeting Hub gene.Results 815 and 22 OP and RA differential genes were screened by GEO database,4463 OP-related targets and 1135 RA related targets were obtained from GeneCards database,4968 OP-related targets and 1144 RA related targets were obtained after combined and de-duplicating,respectively,and 673 overlapping targets were mapped by the two groups.Ten Hub genes were screened by degree≥10.GO functional analysis obtained 964 biological processes(BP),34 cell components(BP)and 50 molecular functions(MF)related to OP and RA.144 KEGG pathways were enriched.Further,28 Chinese traditional medicine active ingredients,including resveratrol,quercetin and curcumin,which may target OP and RA,were screened out.Conclusion The occurrence and development of OP and RA involve many targets and pathways,among which 10 Hub genes such as STAT3,MAPK1 etc.are closely related to OP and RA.These common targets may be through IL-17,Toll-like receptor,Th17 cell differentiation,T cell receptor,HIF-1,MAPK,osteoclast differentiation and other pathways to regulate the occurrence and development of OP and RA.And 28 potential active ingredients of traditional Chinese medicine were exca

关 键 词：骨质疏松症 类风湿性关节炎 生物信息学 Hub基因 中药活性成分 

分 类 号：R684.3[医药卫生—骨科学]