【摘要】 【目的】基于网络药理学探讨关节康治疗骨性关节炎的作用机制。【方法】通过中药系统药理学数据库(TCMSP)和中药系统药理学成分分析数据库(BATMAN-TCM)预测获得关节康的有效化合物及靶点基因,利用GeneCards和在线人类孟德尔遗传数据库(OMIM)获得骨性关节炎疾病的相关靶点基因,取关节康-骨性关节炎疾病交集基因。然后,应用STRING在线数据库构建蛋白相互作用网络(PPI),并筛选出关键基因,再将关键基因输入Cytoscape 3.7.2软件以构建关节康-靶点-骨性关节炎可视化网络。最后,借助DAVID在线工具进行交集靶点的基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。【结果】共预测到关节康的有效化合物95个,其对应的作用靶点共257个,与骨性关节炎疾病密切相关的靶点共有2 868个,获得关节康-骨性关节炎疾病交集靶点共109个,从中筛选出38个关键靶点。GO分析结果显示,关节康-骨性关节炎交集关键基因的生物过程主要是RNA聚合酶Ⅱ启动子转录的正调控、一氧化氮(NO)生物合成过程的正调控、细胞对脂多糖的反应、血管生成、基因表达的正调控、序列特异性DNA结合转录因子活性的正调控、细胞增殖的正调控等。KEGG富集分析结果显示,关节康-骨性关节炎交集关键基因的网络信息通路主要涉及癌症通路、南美锥虫病(美洲锥虫病)、肿瘤坏死因子(TNF)信号通路、缺氧诱导因子1(HIF-1)信号通路、膀胱癌、百日咳、乙型肝炎、利什曼病、沙门氏菌感染、癌症中的蛋白多糖等。【结论】基于网络药理学在分子水平进一步揭示了关节康治疗骨关节炎的作用机制,即通过癌症通路、TNF、HIF-1、NO生物合成过程的正调控、血管生成、RNA聚合酶Ⅱ启动子转录的正调控和细胞对脂多糖的反应等治疗OA,能为后续研究关节康治疗骨关节炎的相关机制等提供新的方向。更多还原

【Abstract】 Objective To explore the mechanism of Guanjie Kang for the treatment of osteoarthritis based on network pharmacology. Methods The effective compounds and target genes of Guanjie Kang were achieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM), the related target genes of osteoarthritis disease were obtained by GeneCards and Online Mendelian Inheritance in Man(OMIM),and then Guanjie Kang-osteoarthritis disease intersection genes were obtained. Next, the protein-protein interaction network(PPI)was constructed by using STRING online database,and the key genes were screened out,and then the key genes were input into Cytoscape 3.7.2 software to build Guanjie Kang-target-osteoarthritis network. Finally,the intersection targets were given analysis of gene ontology(GO)function and enrichment of Kyoto encyclopedia of genes and genomes(KEGG)pathway by David online tool. Results A total of 95 effective compounds of Guanjie Kang were predicted, involving 257 corresponding targets, and 2 868 targets closely related to osteoarthritis were screened out. A total of 109 targets of Guanjie Kang-osteoarthritis disease intersection were obtained,in which 38 key targets were screened out. GO analysis results showed that the biological process of Guanjie Kang-osteoarthritis key intersection genes mainly included positive regulation of transcription from RNA polymerase Ⅱ promoter, positive regulation of nitric oxide(NO) biosynthetic process, cellular response to lipopolysaccharide, angiogenesis, positive regulation of gene expression, positive regulation of sequencespecific DNA binding transcription factor activity,positive regulation of cell proliferation,etc.. KEGG enrichment analysis showed that the network information pathway of Guanjie Kang osteoarthritis intersection key genes mainly involved in pathways in cancer, Chagas disease(American trypanosomiasis), tumor necrosis factor(TNF)signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,bladder cancer,pertussis,hepatitis B, leishmaniasis, salmonella infection, proteoglycan in cancer, etc.. Conclusion These results further reveal the mechanisms of Guanjie Kang for the treatment of osteoarthritis at the molecular level based on network pharmacology, through cancer pathways, TNF, HIF-1, positive regulation of NO biosynthetic process,angiogenesis, positive regulation of transcription from RNA polymerase Ⅱ promoter, and cellular response to lipopolysaccharide,which can provide a new direction for the follow-up study of the treatment of osteoarthritis.更多还原