摘要: 目的：运用网络药理学探讨黄芪–茯苓药对治疗肝纤维化的作用机制。方法：利用中医药系统药理学数据库与分析平台(TCMSP)分别检索黄芪、茯苓的活性成分和有效作用靶点信息，分别通过DrugBank、GeneCards、OMIM和PharmGKB数据库检索肝纤维化疾病靶点，通过微生信–在线生物信息分析平台对已检索的药物作用靶点和疾病靶点取交集，利用Cytoscape 3.10.1软件构建“药物–活性成分–靶点”网络图。并通过STRING数据库对交集靶点进行蛋白互作网络(PPI)分析，计算出核心靶点相关信息，将核心靶点分析结果导入Cytoscape 3.10.1软件构建核心靶点PPI网络，利用Metascape数据库进行GO生物过程与KEGG通路富集分析，将所分析结果通过微生信–在线生物信息分析、可视化云平台制作富集分析图，研究其作用机制。结果：黄芪–茯苓药对共筛选出活性成分35种，靶点207个，肝纤维化疾病靶点共1347个，对药物和疾病靶点分别删除重复值后取交集，黄芪–茯苓药对和肝纤维化的交集靶点共103个，通过对PPI网络分析，二者核心靶点主要是TNF、AKT1、IL-6、IL1B、TP53等。GO富集分析发现，富集的生物过程主要包括细胞迁移、对激素的反应、对细菌分子的反应、对细胞因子刺激的反应、正调控磷代谢过程等方面。KEGG通路富集分析发现了癌症通路、糖尿病并发症中的AGE-RAGE信号通路、PI3K-Akt信号通路、化学致癌作用——受体激活通路等。黄芪–茯苓通过调控癌症通路、糖尿病并发症中的AGE-RAGE信号通路、PI3K-Akt信号通路等发挥治疗肝纤维化的作用。结论：该研究预测了黄芪–茯苓药对可能通过某些靶点及通路对肝纤维化起治疗作用。

Abstract: Objective: The mechanism of astragalus and poria in treating liver fibrosis was studied by network pharmacology. Method: Active ingredients and effective target information of Astragalus and poria were retrieved using TCM Systematic Pharmacology database and Analysis Platform (TCMSP), and liver fibrosis disease targets were retrieved through DrugBank, GeneCards, OMIM and PharmGKB databases, respectively. Cytoscape 3.10.1 software was used to construct the “drug-active ingredients-target” network diagram by taking the intersection of drug action targets and disease targets retrieved on the Weishengxin online biological information analysis platform. In addition, the protein interaction network (PPI) analysis of intersecting targets was carried out using STRING database to calculate the relevant information of core targets. The core target analysis results were imported into Cytoscape 3.10.1 software to build core target PPI network, and the enrichment analysis of GO biological process and KEGG pathway was carried out using Metascape database. The results were analyzed by using Weisheng online bioinformation analysis and visualization cloud platform to make enrichment analysis diagram and study its mechanism. Results: A total of 35 active ingredients with 207 targets and 1347 targets of liver fibrosis disease were screened out for Astragalus and Tuckahoe drug pairs. Overlapping values were deleted for drug and disease targets, and 103 overlapping targets of Astragalus and Tuckahoe drug pairs with liver fibrosis were selected. Through PPI network analysis, the core targets are TNF, AKT1, IL-6, IL1B, TP53 and so on. GO enrichment analysis showed that the biological processes of enrichment mainly included cell migration, response to hormones, response to bacterial molecules, response to cytokine stimulation, and positive regulation of phosphorus metabolism. KEGG pathway enrichment analysis found cancer pathway, AGE-RAGE signaling pathway in diabetes complications, PI3K-Akt signaling pathway, chemical carcinogenity-receptor activation pathway, etc. Astragalus and poria played a role in the treatment of liver fibrosis by regulating the cancer pathway, AGE-RAGE signaling pathway and PI3K-Akt signaling pathway in diabetes complications. Conclusion: This study predicted that Astragalus and poria might have therapeutic effects on liver fibrosis through some targets and pathways.