基于网络药理学和生物信息学研究丹参治疗骨关节炎的分子机制

Molecular Mechanism of Salvia Miltiorrhiza in Treating Osteoarthritis Based on Network Pharmacology and Bioinformatics

目的通过网络药理学和生物信息学方法探讨丹参治疗骨关节炎(OA)的潜在活性成分及作用机制。方法通过检索中药系统药理学数据库和分析平台(TCMSP)中丹参成分,筛选丹参活性成分和作用靶点;检索DisGeNET、Drug bank、OMIM、TTD、Gene Cards、GAD、HPO、PharmGKB、Uniprot疾病数据库中OA相关靶点;检索GEO数据库,多基因芯片联合分析,筛选OA差异表达基因。构建丹参活性成分、丹参作用靶点及OA相关靶点间的相互关系网络,通过网络拓扑分析,筛选丹参治疗OA关键靶点,构建蛋白互作(PPI)网络;采用GO功能和KEGG信号通路富集,分析丹参治疗OA的作用机制,利用分子对接技术验证成分与靶点的结合作用。结果共筛选出57个丹参活性成分,382个OA差异表达基因和68个丹参活性成分与OA共同靶点。结论丹参治疗OA具有多成分、多靶点、多通路的潜在作用机制,为后续丹参与OA的实验和临床研究提供了思路。

Objective To explore the potential active ingredients and mechanism of Salvia miltiorrhiza in the treatment of osteoarthritis(OA)by network pharmacology and bioinformatics methods.Methods All ingredients of Salvia miltiorrhiza were screened to select its active ingredients and therapeutic targets by searching traditional Chinese medicine system pharmacology database and analysis platform(TCMSP).The known OA-related targets were screened from disease databases DisGeNET,Drugbank,OMIM,TTD,Gene Cards,GAD,HPO,PharmGKB,and Uniprot.The differentially expressed genes of OA were screened by retrieving GEO database and analysis of multi microarrays.The network of interaction between active ingredients and therapeutic targets of Salvia miltiorrhiza and known OA-related action targets was built.The key targets of Salvia miltiorrhiza in the treatment of OA were screened by network topology analysis,and the protein-protein interaction network(PPI)was constructed.The mechanism of Salvia miltiorrhiza in treating OA was analyzed by gene ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The binding of Salvia miltiorrhiza ingredients to OA targets was verified by molecular docking technique.Results A total of 57 active ingredients of Salvia miltiorrhiza,382 differentially expressed genes of OA,and 68 common targets of Salvia miltiorrhiza active ingredients and OA were screened.Conclusion Salvia miltiorrhiza has the potential mechanism of multi-ingredient,multi-target and multi-channel in the treatment of OA,which provides ideas for the subsequent experiment and clinical research of Salvia miltiorrhiza in treating OA.