基于网络药理学探究芍药甘草汤治疗肾绞痛的作用机制

Discussion on the Treatment of Renal Colic with Shaoyao Gancao Decoction Based on Network Pharmacology

摘要: 目的：通过网络药理学探究芍药甘草汤有效成分、肾绞痛之间的网络关系，探究芍药甘草汤的作用机制。方法：通过中药系统药理学数据库分析平台(TCMSP)筛选芍药苷草汤有效成分及相应的靶点；从GeneCards、DisGeNET、OMIM、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：芍药甘草汤93种活性成分，共作用于228个靶点；疾病靶点549个，疾病和药物交集靶点41个；核心靶点包括血管内皮生长因子A (VEGFA)、前列腺素内过氧化物合酶-2 (PTGS2)、白细胞介素6 (IL6)、白介素-1β (IL1β)、肿瘤坏死因子(TNF)等；GO富集分析在BP上主要为炎症反应、血液循环等的生物学过程，在CC上表现为膜筏、膜筏、膜微区等结构的细胞定位，在MF上表现为细胞因子活性、受体配体活性、信号受体激活剂活性等分子功能；KEGG富集分析主要包括AGE-RAGE、缺氧诱导因子1、白细胞介素-17等通路。结论：芍药甘草汤有效成分可能通过炎症相关通路作用，缓解炎性因子相关性疼痛，从而达到治疗肾绞痛的目的。

Abstract: Objective: To investigate the network relationship between the active ingredients of peony and licorice soup and renal colic through network pharmacology and to investigate the mechanism of action of peony and licorice soup. Methods: The active ingredients and corresponding targets of Paeonia lactiflora glycyrrhiza tang were screened by the Traditional Chinese Medicine Systematic Pharmacology Database Analysis Platform (TCMSP); the targets related to urinary colic disease were obtained from GeneCards, DisGeNET, OMIM, and databases; the Venn diagram of the intersecting targets of drugs, diseases was drawn using the online software platform Venny 2.1; the Venn diagram of the intersecting targets was obtained by Metoscape database to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets; building PPI networks through STRING online database, while importing Cytoscape 3.9.1 to obtain core targets; mapping active ingredient-target networks through Cytoscape 3.9.1. Results: There were 93 kinds of Peony and licorice decoction active ingredient, acting on 228 targets; There were 549 disease targets and 41 disease and drug intersection targets; core targets include vascu-lar endothelial growth factor A (VEGFA), prostaglandin endoperoxidase-2 (PTGS2), interleukin 6 (IL6), interleukin-1β (IL1β), tumour necrosis factor (TNF), etc. GO enrichment analysis is mainly for biological processes such as inflammatory response and blood circulation on BP, cellular localiza-tion of structures such as membrane rafts, membrane rafts and membrane micro-regions on CC, and molecular functions such as cytokine activity, receptor ligand activity and signal receptor activator activity on MF; KEGG enrichment analysis mainly includes AGE-RAGE, hypoxia-inducible factor 1, interleukin-17, etc. pathways. Conclusion: The active ingredients of Paeonia lactiflora and Glycyrrhiza glabra soup may act through inflammation-related pathways to relieve inflammatory factor-associated pain, thereby achieving the treatment of renal colic.