摘要
目的利用生物信息学及分子对接技术探究红花化瘀汤干预骨关节炎的相关分子机制研究。方法通过NCBI GEO数据库获取骨关节炎相关芯片,利用R语言进行差异基因表达分析。借助GeneCards数据库对骨关节炎靶基因进行检索与筛选,并与差异表达基因合并去重,对骨关节炎疾病靶基因进行预测。运用TCMSP数据库对红花化瘀汤主要有效成分及作用靶基因进行筛选和挖掘,构建药物与疾病映射靶基因的PPI网络,通过David数据库对关键靶基因进行GO生物过程及KEGG通路富集分析。最终将中药中主要有效成分与关联度较高的关键靶基因进行分子对接。结果共筛选出红花化瘀汤药物活性成分110个;与骨关节炎的共同靶点23个,核心靶点为IL-6、PTGS2、IL-1B、MMP2、VEGFA;GO分析结果得出,红花化瘀汤治疗骨关节炎的机制主要和缺氧、炎症反应、骨代谢、微循环等生物过程密切相关;根据KEGG富集分析显示类风湿性关节炎、肿瘤坏死因子信号通路、toll样受体信号通路等是红花化瘀汤治疗骨关节炎的主要信号通路;分子对接结果表明槲皮素、山柰酚、鼠尾草酚酮可靶向调节MMP2、PTGS2、PTGS2。结论研究证实红花化瘀汤通过控制炎症因子水平、促进软骨细胞死亡等多方面对骨关节炎发挥治疗作用,具有多靶点、多通路的特征;为基础研究与相关临床应用提供新的证据和思路。
Objective To explore the molecular mechanism of Flos Carthami Stasis-Resolving Decoction in the intervention of osteoarthritis by bioinformatics and molecular docking techniques.Methods The osteoarthritis-related chips were obtained from NCBI-GEO database,and differential gene expression was analyzed by R language.The target genes of osteoarthritis were retrieved and screened by GeneCards database,and combined with differentially expressed genes to deduplicate and predict the target genes of osteoarthritis.The main effective components and target genes of Flos Carthami Stasis-Resolving Decoction were screened and mined by TCMSP database,and the PPI network of drug-disease mapping target genes was constructed.The GO biological process and KEGG pathway enrichment of key target genes were carried out though David database.Finally,the main active ingredients in traditional Chinese medicine were molecularly docked with the key target genes with high correlation.Results A total of 110 active ingredients of Flos Carthami Stasis-Resolving Decoction were screened out.Among them,there were 23 common targets with osteoarthritis,and the core targets were IL-6,PTGS2,IL-1 B,MMP2 and VEGFA.The results of GO analysis showed that the mechanism of Flos Carthami Stasis-Resolving Decoction in treating osteoarthritis was mainly closely related to biological processes such as hypoxia,inflammatory response,bone metabolism,and microcirculation.According to KEGG enrichment analysis,rheumatoid arthritis,tumor necrosis factor signaling pathway and toll-like receptor signaling pathway,etc.were the main signaling pathways of Flos Carthami Stasis-Resolving Decoction in the treatment of osteoarthritis.Molecular docking results showed that quercetin,kaempferol and sage phenolone could target to regulate MMP2,PTGS2 and PTGS2.Conclusion It is proved that Flos Carthami Stasis-Resolving Decoction plays a therapeutic role in the treatment of osteoarthritis by controlling the level of inflammatory factors and promoting the death of chondrocytes.It ha
作者
刘国强
王桂香
刘琳琳
刘丹
季文辉
潘浩
Liu Guo-qiang;Wang Gui-xiang;Liu Lin-lin;Liu Dan;Ji Wen-hui;Pan Hao(Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Cangzhou Hebei 061000)
出处
《世界中西医结合杂志》
2022年第6期1143-1149,1154,共8页
World Journal of Integrated Traditional and Western Medicine
基金
河北省中医药科研计划项目(2022229)。
关键词
红花化瘀汤
骨关节炎
生物信息学
基因芯片
分子对接
Flos Carthami Stasis-Resolving Decoction
Osteoarthritis
Bioinformatics
Gene chips
Molecular docking
