基于网络药理学探究复方双金颗粒治疗泌尿系结石作用机制

Explore the Mechanism of Compound Shuangjin Granules in the Treatment of Urinary Calculi Based on Network Pharmacology

摘要: 目的：通过网络药理学探究复方双金颗粒有效成分、泌尿系结石之间的网络关系，探究复方双金颗粒作用机制。方法：通过中药系统药理学数据库分析平台(TCMSP)、中药分子机制的生物信息分析工具(BATMAN-TCM)筛选复方双金颗粒有效成分及相应的靶点；从GeneCards、DisGeNET、OMIM、Drugbank数据库中获取泌尿系结石疾病相关靶点；使用在线软件平台Venny2.1绘制药物、疾病的交集靶点维恩图；通过Metoscape数据库对交集靶点进行基因本体功能(GO)和京都基因与基因组百科全书(KEGG)通路富集分析；通过STRING在线数据库构建PPI网络，同时导入Cytoscape3.9.1获取核心靶点；通过Cytoscape3.9.1绘制活性成分–靶点网络。结果：复方双金颗粒129种活性成分，共作用于502个靶点；疾病靶点743个，疾病和药物交集靶点70个；核心靶点包括肿瘤坏死因子(TNF)、血管内皮生长因子A (VEGFA)、核因子红细胞2相关因子2 (NFE2L2)、白细胞介素6 (IL6)、白介素-1β (IL1B)等；GO富集分析在BP上主要为细胞对氧化应激、活性氧、脂质等的生物学过程，在CC上表现为细胞膜、膜微区、膜筏等结构的细胞定位，在MF上表现为肾上腺素能受体、细胞因子、配体激活转录因子等分子功能；KEGG富集分析主要包括流体剪切应力和动脉粥样硬化、AGE-RAGE、癌症、钙信号通路、肿瘤坏死因子等通路。结论：复方双金颗粒有效成分可能通过各类氧化应激、炎症相关通路作用于泌尿系结石。

Abstract: Objective: To explore the network relationship between the active components of Compound Shuangjin granules and urinary calculi through network pharmacology, and to explore the mechanism of action of compound Shuangjin granules. Methods: The effective components and corresponding targets of Compound Shuangjin granules were screened by TCMSP and BATMAN-TCM. The targets of urinary calculi disease were obtained from GeneCards, DisGeNET, OMIM and Drugbank databases. Venny2.1, an online software platform, was used to draw the intersection target Venn diagram of drugs and diseases. Metoscape database was used for gene ontology function (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for intersection targets. Construct PPI network through STRING online database and import Cytoscape3.9.1 to obtain core target. Draw the active ingredient-target network via Cytoscape3.9.1. Results: There were 129 active components of Compound Shuangjin granules, which acted on 502 targets. There were 743 disease targets and 70 disease and drug intersection targets. Core targets include tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), nuclear factor erythrocyte 2-associated factor 2 (NFE2L2), interleukin-6 (IL6), interleukin-1β (IL1B), etc. In BP, GO enrichment analysis is mainly the biological process of cells to oxidative stress, reactive oxygen species, lipids, etc. In CC, it is the cell localization of cell membrane, membrane microregion, membrane raft and other structures. In MF, it is the molecular function of adrenergic receptors, cytokines, lig-and-activated transcription factors and so on. KEGG enrichment analysis mainly included fluid shear stress and atherosclerosis, AGE-RAGE, cancer, calcium signaling pathways, tumor necrosis factor and other pathways. Conclusion: The active components of Compound Shuangjin granules may act on urinary calculi through various pathways related to oxidative stress and inflammation.