基于网络药理学探讨清胰汤治疗急性胰腺炎的作用机制

Mechanism of QingyiTang in the treatment of acute pancreatitis based on network pharmacology

目的:基于网络药理学探讨清胰汤(QYT)治疗急性胰腺炎(AP)的作用机制,并结合动物实验验证。方法:通过BATMAN数据库检索QYT中8味中药化合物的作用靶点,Gene Cards数据库检索AP的基因靶点,筛选得到药物与疾病的交集靶点。利用STRING和Cytoscape将交集靶点进行蛋白互作分析,推测核心靶点,构建“中药材-活性化学成分-靶点”网络,并对“药物-疾病”靶点进行GO和KEGG富集分析,得到QYT在治疗AP过程中所涉及的相关重要靶点及通路。利用实验验证QYT在治疗AP中对自噬过程的调控作用。结果:分析发现QYT所含化合物共214种,对AP有效的活性化合物121种,活性化合物对应蛋白靶点删除重复值后得到1853个,AP疾病靶点1000个,“药物-疾病”靶点145个,GO功能富集分析1310条,KEGG通路富集67条(均P<0.05),主要涉及坏死、凋亡、炎症反应、自噬等生物学进程;实验结果证实QYT减轻了AP的病理损害,同时减轻了自噬进程。结论:网络药理学揭示QYT主要通过减少自噬,调节炎症因子,改善微循环障碍和肠屏障损伤等方式治疗AP,具有多靶点、多组分的潜在机制。经动物实验验证,QYT可能通过调控自噬发挥效用。

Objective:To investigate the mechanisms underlying QingyiTang in treatment of acute pancreatitis by using a network pharmacology approach and to validate by experimental test.Methods:The targets of the eight Chinese herbal compounds in QingyiTang were searched by BATMAN database,and the gene targets of acute pancreatitis were searched by Gene Cards database,and the intersection targets of drugs and diseases were screened.STRING and Cytoscape were used to analyze the protein interactions of the intersecting targets,the core targetswereinferred,and the"Chinese herbal medicine-active chemical component-target"network was constructed,and GO and KEGG enrichment analysis on the"drug-disease"targets to obtain the important targets and pathways involved in the treatment of acute pancreatitis with QingyiTang.The regulation of autophagy process in the treatment of acute pancreatitis by using Qingyi Tang was validated.Results:A total of 214 compounds in QingyiTang were analyzed,and 121 active ingredients were found to have the rapeutic effects on acute pancreatitis.After removing duplicates,obtained 1853 protein targets of active compounds,1000 acute pancreatitis disease targets,145 drug-disease intersection targets,1310 GO items and 67 KEGG pathways(all P<0.05),which mainly involved biological processes such as necrosis,apoptosis,inflammatory response,and autophagy.With these results,this study focused on the treatment of acute pancreatitis by QingyiTang through autophagic process,and the experimental results confirmed that QingyiTang reduced the pathological damage of acute pancreatitis while mitigating the autophagic process.Conclusion:The potential mechanism of QingyiTang for treating acute pancreatitis with multi-target and multi-component is revealed by network pharmacology,mainly through reducing autophagy,regulating inflammatory factors,improving microcirculatory disorders and intestinal barrier damage.The effectiveness is verified by animal experiments and QingyiTang may be exerted through regulating autophagy.