基于网络药理学及分子对接探讨血必净注射液治疗重症急性胰腺炎的潜在作用机制

The Potential Mechanism of Xuebijing Injection in Treatment of Severe Acute Pancreatitis Based on Network Pharmacology and Molecular Docking

摘要: 血必净注射液是中医中药推广应用治疗手段，为研究其在重症急性胰腺炎中治疗靶点、机制，结合目前常用复方研究的网络药理学及分子对接技术探讨血必净注射液治疗重症急性胰腺炎的潜在作用机制。检索TCMSP数据库血必净注射液的药物活性成分及作用靶点，利用GeneCards数据库筛选重症急性胰腺炎的疾病靶点，将两者Cytoscape 3.7.0软件构建“药物–成分–潜在靶点”网络，将潜在靶点导入STRING数据库、再经Cytoscape 3.7.0构成蛋白互作网络，筛选关键靶点，进行GO及KEGG富集分析。筛选获得血必净注射液有效活性成分123个，靶点249个，与重症急性胰腺炎共同靶点74个，其中关键靶点涉及AKT1、TP53、VEGFA、TNF、IL6、MMP9等。GO富集得到647个生物学过程，KEGG通路富集得到97条信号通路，选取PI3K-Akt信号通路预测血必净注射液治疗重症急性胰腺炎的作用机制。分子对接验证AKT1、TP53、VEGFA关键靶点与quercetin、luteolin、beta-sitosterol有较好结合力。血必净注射液可能通过抗炎、抗氧化等方面直接或间接对重症急性胰腺炎起到治疗作用。

Abstract: This study is to explore the potential mechanism of Xuebijing Injection in the treatment of severe acute pancreatitis by network pharmacology and molecular docking technology. The active components and action targets of Xuebijing Injection were searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the related targets of severe acute pancreatitis were screened by Gene Cards database. The “drug component potential target” network was constructed by using Cytoscape 3.7.0 software, and the potential targets were imported into STRING to obtain protein-protein interaction (PPI) network, which was imported into Cytoscape 3.7.0 to screen key targets. David database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. A total of 123 active components of Xuebijing Injection were screened. 249 corresponding targets and 74 common targets were obtained with severe acute pancreatitis, of which the key targets included AKT1, TP53, VEGFA and so on. GO and KEGG enrichment analysis yielded 647 biological processes and 97 signal pathways. PI3K-Akt signal pathway was selected to predict the potential mechanism of Xuebijing Injection in the treatment of severe acute pancreatitis. Molecular docking verified that the key targets of AKT1, TP53 and VEGFA had good binding force with quercetin, luteolin and beta sitosterol. The analysis based on network pharmacology and molecular docking uncovered that Xuebijing Injection may have a direct or indirect therapeutic effect on severe acute pancreatitis through anti-inflammatory and anti-oxidation.