| 邹阳,王伟东.基于网络药理学探究右归饮在骨性关节炎软骨下骨中的核心靶点[J].浙江中西医结合杂志,2024,34(12): |
| 基于网络药理学探究右归饮在骨性关节炎软骨下骨中的核心靶点 |
| Exploration on the key therapeutic targets of Yougui drink in subchondral bone of osteoarthritis based on network pharmacology |
| 投稿时间:2024-04-03 修订日期:2024-07-26 |
| DOI: |
| 中文关键词: 右归饮 骨性关节炎 软骨下骨 网络药理学 |
| 英文关键词:Yougui drink Osteoarthritis Subchondral bone Network pharmacology |
| 基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目) |
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| 中文摘要: |
| 目的 通过网络药理学分析右归饮在骨性关节炎(Osteoarthritis, OA)软骨下骨中的核心靶点与功能通路,从而探索右归饮在OA软骨下骨中的作用机制。方法 通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)查询右归饮中的中药相关的活性成分和药物靶点,再基于GeneCards数据库筛选右归饮活性成分与OA疾病的靶点交集,获取右归饮在OA中潜在的治疗靶点。然后利用基因本体论(Gene Ontology, GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)进行富集分析,获取相关的条目和功能通路,再使用相互作用基因/蛋白质的搜索工具(Search Tool for the Retrieval of interacting Genes/Proteins, STRING) 数据库进行核心靶点的筛选。依靠基因表达汇编(Gene Expression Omnibus, GEO)数据库对胫骨内侧和胫骨外侧的软骨下骨样本进行测序,共50例样本,其中健康对照(Control)10例,OA样本(Case)40例。在转录组数据集中,可视化核心靶点的组间表达情况。最后基于组间差异显著的核心靶点,构建其相关的中药-活性成分-药物靶点网络。 结果 基于TCMSP和GeneCards数据库,共获得25个OA中的潜在的右归饮治疗靶点,对潜在靶点进行功能富集,在GO中,共富集到1396个条目,在KEGG中,共富集到84个功能通路。构建潜在靶点的蛋白互作网络(Protein-Protein Interaction, PPI),包含25个点和249条边,获得5个核心靶点。在转录组数据集中,可视化5个核心靶点的组间表达情况(Control vs Case),其中肿瘤坏死因子(Tumor Necrosis Factor, TNF)、基质金属蛋白酶9 (Matrix Metalloproteinase 9, MMP 9)、转化生长因子-β1 (Transforming growth factor-β1,TGF-β1)的组间差异显著且表达趋势一致,均为上调基因(Case组表达高于Control组)。构建TNF、MMP9、TGFβ1相关的中药-活性成分-药物靶点网络,网络中包含5味中药、5个活性成分和3个药物靶点。结论 本研究获得了3个OA软骨下骨中右归饮相关的核心靶点,探究了相关功能和作用网络,可有助于右归饮作用于OA软骨下骨的机制探索。 |
| 英文摘要: |
| Objective To explore the key therapeutic targets and mechanism of Yougui drink in subchondral bone of osteoarthritis (OA) bsaed on network pharmacology. Methods The acitve ingredients and drug targets of Yougui drink were searched by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Based on the GeneCards database, potential therapeutic targets of Yougui drink on OA were obtained. Then, the GO and KEGG pathway enrichment analysis of key targets were performed, and the STRING database was used to plot the protein interaction (PPI). Depending on the GEO database, 50 subchondral bone samples were sequenced including 10 healthy controls (Control) and 40 OA samples (Case). The inter group expression of key targets was visualized in the transcriptome dataset, and based on the significant inter group differences, the network of related active ingredient drug targets is constructed. Results There were 25 potential targets of Yougui drink for treating OA disease. GO enrichment analysis is obtained 1396 cell biological items, and 84 related signaling pathways were obtained by KEGG pathway enrichment analysis. Five key targets were obtained in the PPI network, and the inter group difference of TNF, MMP9, and TGF-β1 is significant, all of which are upregulated genes (the expression in the Case group is higher than that in the Control group). The network of related active ingredient drug targets is constructed with 5 herbs, 5 active ingredients and 3 drug targets. Conclusion The present study identified 3 key therapeutic targets of Yougui drink in the subchondral bone of OA and explored their functions and action networks, which may contribute to the exploration of the mechanism by which Yougui drink acts on the subchondral bone of OA. |
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