[关键词]
[摘要]
目的 运用计算机网络药理学技术预测桃核承气汤治疗脓毒症心肌功能障碍的作用靶点和信号通路,进一步分析其防治脓毒症心肌功能障碍的基础和作用机制。方法 运用中药系统药理学成分分析平台Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)数据库获取桃核承气汤的有效成分及作用靶标基因,从GeneCards数据库收集脓毒症心肌功能障碍的靶标基因,将两者取交集后得到疾病-药物蛋白靶基因,运用STRING构建蛋白质间相互作用网络,并通过Cytoscape软件将结果进行网络可视化展示,通过网络结构和节点间加权重联系的计算分析算法筛选出作用的关键基因。借助Webgestalt在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并可视化展示。最后利用CTD数据库并结合文献学习,获取关键基因于脓毒症心肌功能障碍的疾病治疗作用。结果 桃核承气汤的135个化合物中有64成分通过20个靶点与脓毒症心肌功能障碍相互关联。其中AKT1、HMOX1、JUN、TNF、IL1B、MAPK14、NOS3、PPARG、ICAM1、NOS2、VCAM1、STAT1等关键基因主要通过调控炎症反应、促进细胞存活、抗细胞凋亡、参与能量代谢、病原识别、毒物代谢等路径,在质膜、细胞膜、吞噬细胞、线粒体自噬等分子反应中发挥作用。结论 网络药理学方法科学预测桃核承气汤防治脓毒症心肌功能障碍的关键靶标及其参与的相关通路,提示该方剂对脓毒症心肌功能障碍的防治作用为多靶点、多通路、多选择的复杂机制,并且多与抗炎、抗细胞凋亡、促进细胞存活等机制相关。
[Key word]
[Abstract]
Objective To explore the potential therapeutic targets of Taohe Chengqi Decoction for sepsis-induced myocardial dysfunction based on network pharmacology. Methods The active constituents and target genes of Taohe Chengqi Decoction were screened based on TCMSP and Uniprot database. Target genes of sepsis-induced myocardial dysfunction were screened by gene cards database, and the intersection between the targets associated with the components of Taohe Chengqi Decoction and sepsis-induced myocardial dysfunction was performed and visualized by Venn diagram. Cytoscape software was used to construct ‘active component-target’ interaction network diagram. The same target genes were uploaded to the STRING database, the protein interaction network map (PPI) was constructed, and core genes were screened by using R language. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment of key targets were analyzed using functional enrichment analysis web tool Webgestalt 2019. Results The 64 active components and 20 effective targets of Taohe Chengqi Decoction in the treatment of sepsis-induced myocardial dysfunction were predicted. Core genes in PPI network are RAC-alpha serine/threonine-protein kinase(AKT1), Heme oxygenase 1(HMOX1), Transcription factor AP-1(JUN), etc. GO enrichment analysis shows that it can affect acute inflammatory response, muscle cell proliferation, reactive oxygen species metabolic process, extrinsic apoptotic signaling pathway, etc. Enrichment analysis of KEGG pathway showed that AGE-RAGE signaling pathway in diabetic complications and fluid shear stress and atherosclerosis pathways were the most significant pathways, followed by TNF signaling pathway and Toll-like receptor signaling pathway. Conclusions Based on network pharmacology, Taohe Chengqi Decoction can treat sepsis-induced myocardial dysfunction by multiple targets and multiple pathways, such as anti-inflammatory, anti-apoptosis, promote cell survival.
[中图分类号]
R285.5
[基金项目]
国家中医药管理局“西学中”骨干人才培训项目;江苏省中医药局科技项目(JD2019SZ03)