基于网络药理学分析石上柏抗心肌缺血的作用机制研究

Network Pharmacology-Based to Analyze Screen Selaginella Doederleinii’s against Myocardial Ischemia

摘要: 目的：借助网络药理学筛选石上柏抗心肌缺血的潜在信号通路及靶点，并探究石上柏抗心肌缺血的潜在作用机制。方法：通过TCMSP平台和相关文献根据口服生物利用度、类药性筛选获取石上柏化合物；利用数据库(PubChem、Swiss Target Prediction, Gene Cards)预测化合物靶点与疾病靶点；运用Cytoscape 3.7.2构建“成分–靶点”网络；采用Bioinformatics做出两者交集靶点的韦恩图并构建PPI网络进行GO和KEGG富集分析。结果：筛选出17个石上柏化合物，395个作用靶点，其中抗心肌缺血靶点120个；石上柏抗心肌缺血主要作用VEGFA、TNF、TP53、PTGS2、JUN等靶蛋白；GO分析中，生物途径涉及MAPK级联反应的调控，细胞组分包括膜阀、膜微区，分子功能分析中有受体、酶、转录因子参与；KEGG富集通路共286条，其中重要通路有AGE-RAGE信号通路、神经活性配体–受体相互作用通路。结论：研究表明石上柏中穗花杉双黄酮、芹菜素、大麦芽碱等可能对心肌缺血有治疗作用。初步推测出石上柏抗心肌缺血主要靶基因和通路，为石上柏抗心肌缺血研究提供新方向。

Abstract: Objective: To explore the potential signaling pathways and mechanism of Selaginella doederleinii’s anti-myocardial ischemia using network pharmacology. Methods: the compounds about Selaginella doederleinii were obtained through the TCMSP and related literature and screened according to the oral bioavailability and drug-like properties; the databases (Pub Chem, Swiss Target Prediction, Gene Cards) were used to predict compound targets and the disease targets, then by the Bioinformatics and “component-target” network was constructed by Cytoscape 3.7.2; finally, a Wayne diagram of the intersection targets was made at Bioinformatics and a PPI network was constructed for GO and KEGG enrichment analysis. Results: There were 17 Selaginella doederleinii compounds and 395 targets of which included 120 anti-myocardial ischemia targets. The main anti-myocardial ischemia proteins are VEGFA, TNF, TP53, PTGS2, and JUN. In GO analysis biological pathways involved the regulation of the MAPK cascade; cell components comprised membrane valves, membrane microdomains; molecular function analysis involved receptors, enzymes, and transcription factors. There were 286 KEGG enrichment pathways, among which the important pathways were the AGE-RAGE signaling pathway in diabetic complications and neuroactive ligand-receptor interaction etc. Conclusion: The research suggested that by network pharmacology, amentoflavone, apigenin, hordenine, etc. might have therapeutic effects on myocardial ischemia. The main target genes and pathways of resistance to myocardial ischemia were preliminarily predicted, which provided a new direction for the study of resistance to myocardial ischemia.