基于生物信息学的青藤碱治疗类风湿关节炎作用机制研究

Research on Mechanism of Sinomenine in Treating Rheumatoid Arthritis via Bioinformatics

目的:通过分子反向对接和网络药理学预测青藤碱(SN)治疗类风湿关节炎(RA)的潜在靶点、通路,探究SN治疗RA的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)评估SN的可药性,将药物再定位及药物不良反应预测服务器(DRAR-CPI)预测出的SN潜在靶点与DisGeNET数据库中查询到的RA靶点作交集,以获取SN治疗RA的潜在靶点,利用GeneMANIA构建靶点间相互关系网络及筛选hub靶点,利用KOBAS 3.0和Omicshare平台工具等进行基因本体(GO)、京都基因与基因百科全书(KEGG)通路富集分析。结果:SN的理化性质表明其具有良好的可药性。预测出SN治疗RA的潜在靶点47个,相关潜在靶点间存在共表达特征、可预测到的相互作用关系等关联,并筛选出蛋白激酶B1(AKT1)、肿瘤蛋白p53(TP53)、硫氧还蛋白(TXN)3个hub靶点。GO富集结果涉及16个生物学过程、7个分子功能及10个细胞组件,KEGG显著富集通路的前10条通路包括细胞凋亡通路、肿瘤坏死因子(TNF)信号通路、低氧诱导因子1(HIF-1)信号通路、Ras相关蛋白1(Rap1)信号通路等。结论:SN可能通过作用于AKT1、TP53、TXN、白细胞介素-10(IL-10)、丝裂原活化蛋白激酶14(MAPK14)等靶点及细胞凋亡、TNF信号通路、HIF-1信号通路、相关蛋白Rap1信号通路等通路影响RA的疾病过程,为后期相关实验验证及临床应用研究提供了数据支撑。

Objective:Using reverse molecular docking and network pharmacological technology to predict the potential targets and signaling pathways of sinomenine(SN)in treating rheumatoid arthritis(RA)and further investigate its mechanism in RA.Methods:TCMSP was used to evaluate the druggability of SN;the potential SN targets for RA treatment was acquired through the intersection of potential SN targets predicted by DRAR-CPI and RA targets was predicted by DisGeNET;GeneMANIA was used to build target interaction network and screen hub targets;KOBAS 3.0 and Omicshare Tools was used for the enrichment analysis of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways,and then drawing.Results:It was indicated by the physicochemical properties of SN that SN has the good druggability.47 potential SN targets for RA treatment were predicted,the co-expression,predictable interaction and other relations of relevant target genes were found in relevant potential targets,and protein kinase B1(AKT1),cell tumor antigen p53(TP53),and thioredoxin(TXN)were screened as hub targets.The results of gene ontology enrichment involved 16 biological processes,7 molecular functions and 10 cellular components.The top 10 significantly enriched in KEGG pathways included apoptosis pathway,TNF signaling pathway,HIF-1 signaling pathway and Rap1 signaling pathway.Conclusion:SN might influence the disease process of RA through genes including AKT1,TP53,TXN,interleukin-10(IL-10),mitogen-activated protein kinase 14(MAPK14)and pathways including apoptosis pathway,TNF signaling pathway,HIF-1 signaling pathway and Rap1 signaling pathway.This provides data support for further experimental validation and research on clinical application.