基于网络药理学及分子对接技术探讨刺梨干预脓毒症的作用

The Preventive Effect of Rosa Roxburghii in Treating Sepsis Based on Network Pharmacology and Molecular Docking Technology

目的:借助网络药理学及分子对接技术探讨刺梨干预脓毒症的作用机制,为扩大刺梨用药范围提供依据.方法:通过文献研究及Swiss数据库筛选刺梨活性成分并分析相关作用蛋白靶点,借助OMIM、Gene Cards、DRUG BANK、DisGeNet等数据库分析脓毒症基因靶点并取交集;借助STRING数据库及CytoScape软件构建PPI网络关系并得到刺梨干预脓毒症关键靶点;借助Metascape数据库进行生物富集分析;使用Schrödinger软件进行核心化合物-蛋白分子对接.结果:得到刺梨核心化合物为57个,涉及132个蛋白靶点,其中与脓毒症相关核心靶点为AKT1、PIK3R1、SRC等;在60组分子对接结果中,所有对接分数均<-4,表明多数化合物-蛋白有较大结合能;KEGG富集分析结果显示关键通路为Phospholipase D signaling pathway和Endocrine resistance pathway.结论:刺梨干预脓毒症依靠多通路、多靶点协调作用,其主要活性成分为槲皮素、鞣花酸、木犀草素,通过AKT1、PIK3R1、SRC等蛋白作用与Phospholipase D signaling pathway和Endocrine resistance pathway等通路发挥治疗脓毒症的干预作用.

Objective:To explore the mechanism of Rosa roxburghii in the treatment of sepsis by means of network pharmacology and molecular docking,and to provide evidence for expanding the scope of Rosa roxburghii.Methods:The active components of Rosa roxburghii were obtained through literature review and Swiss database screening,and the related protein targets were analyzed.The gene targets of sepsis were analyzed by OMIM,GeneCards,DRUG BANK,DisGeNet and other databases,and the intersection was selected.The PPI network relationship was constructed with the help of STRING database and Cyto-scape software,and the key targets of Rosa roxburghii intervention in sepsis were obtained.Bioenrichment analysis was carried out with metascape database.Schrodinger software was used for core compound-protein molecular docking.Results:There were 57 core compounds involving 132 protein targets,among which the core targets associated with sepsis were AKT1,PIK3R1,SRC,etc.In the 60 groups of molecu-lar docking results,all docking fractions were<-4,indicating that most of the compounds had greater binding energy.KEGG enrichment analysis showed that the key pathways were Phospholipase D signaling pathway and Endocrine resistance pathway.Conclusion:The intervention of Rosa roxburghii in sepsis de-pends on multi-pathway and multi-target coordination.The main active components of Rosa roxburghii are quercetin,ellagic acid and luteolin.AKT1,PIK3R1,SRC and other proteins play a role in the treat-ment of sepsis with Phospholipase D signaling pathway and Endocrine resistance pathway.