基于生物信息学技术研究破格救心汤治疗急性心肌梗死合并心源性休克的作用机制

Research on the Mechanism of Poge Jiuxin Decoction in Treating Acute Myocardial Infarction with Cardiogenic Shock Based on Bioinformatics Technology

摘要: 目的：运用生物信息学技术探讨破格救心汤(Poge Jiuxin Decoction, PJD)治疗急性心肌梗死(acute myocardial infarction, AMI)合并心源性休克(cardiogenic shock, CS)的作用机制，为临床研究提供理论依据。方法：借助TCMSP、BATMAN-TCM 2.0和HIT 2.0中药药理学数据库筛选破格救心汤中各个单味药的有效成分和潜在靶点；检索Genecards疾病数据库，分别筛选AMI和CS的疾病靶点；获得破格救心汤治疗AMI合并CS的交集靶点基因。构建PJD有效成分–靶点基因网络并筛选出重要的有效成分；利用String数据库分析靶点间相互作用的PPI网络；对靶点基因进行基因本体(GO)生物学过程分析和京都基因与基因组百科全书(KEGG)通路分析。利用Cytoscape3.8.2软件和R语言软件包对分析结果进行可视化。最后在CB-Dock2平台上对关键成分与核心靶点蛋白进行分子对接验证。结果：预测破格救心汤靶点880个，筛选AMI靶点1274个，CS靶点164个，将三者取交集，获得破格救心汤治疗AMI合并CS靶点共34个。破格救心汤在治疗AMI合并CS中重要的有效成分包括槲皮素、芸香苷等。GO生物学功能主要富集于循环系统中的血管过程、含胶原蛋白的细胞外基质、信号受体激动剂活性等；KEGG通路主要富集于包含细胞因子–细胞因子受体相互作用、恰加斯病、糖尿病并发症中的AGE-RAGE信号通路等疾病相关信号通路。分子对接结果显示槲皮素、芸香苷与核心靶点TNF之间存在较强的结合活性。结论：该研究通过生物信息学方法研究破格救心汤治疗AMI合并CS的作用机制，初步阐明破格救心汤可通过多成分、多靶点和多通路参与治疗AMI合并CS患者，为后续深入研究提供理论基础，但仍需具体实验验证。

Abstract: Objective: To explore the mechanism of Poge Jiuxin Decoction (PJD) in treating acute myocardial infarction (AMI) complicated with cardiogenic shock (CS) using bioinformatics technology, and to provide a theoretical basis for clinical research. Methods: The effective components and potential targets of each single herb in PJD were screened using TCMSP, BATMAN-TCM 2.0, and HIT 2.0 traditional Chinese medicine pharmacology databases; the disease targets of AMI and CS were screened separately using the Genecards disease database; the intersection target genes of PJD in treating AMI combined with CS were obtained. A PJD effective component-target gene network was constructed and important effective components were screened; the PPI network of interactions between target genes was analyzed using the String database; the target genes were subjected to Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The analysis results were visualized using Cytoscape3.8.2 software and R language packages. Finally, molecular docking validation of key components with core target proteins was performed on the CB-Dock2 platform. Results: A total of 880 targets of PJD were predicted, 1274 targets of AMI were screened, and 164 targets of CS were screened. Taking the intersection of the three, a total of 34 targets of PJD in treating AMI combined with CS were obtained. Important effective components of PJD in treating AMI combined with CS include quercetin, rutin, etc. GO biological functions are mainly enriched in vascular processes in the circulatory system, extracellular matrix containing collagen, and signal receptor agonist activity; KEGG pathways are mainly enriched in disease-related pathways including cytokine-cytokine receptor interaction, Chagas disease, and AGE-RAGE signaling pathway in diabetic complications. Molecular docking results show that quercetin, rutin, and the core target TNF have strong binding activity. Conclusion: This study investigated the mechanism of PJD in treating AMI combined with CS through bioinformatics methods, preliminarily clarifying that PJD can participate in the treatment of AMI combined with CS patients through multiple components, multiple targets, and multiple pathways, providing a theoretical basis for subsequent in-depth research, but still requiring specific experimental verification.