目的 利用网络药理学的方法探究瓜蒌皮注射液治疗冠心病稳定型心绞痛的网络调控机制。方法 以方中主要成分兼顾主要结构类型为选取原则，确定了瓜蒌皮注射液19个化合物为研究对象，通过Swiss Target Prediction、TCMSP数据库预测化合物潜在作用靶点，通过GeneCards、DisGeNET、OMIM数据库收集冠心病及稳定型心绞痛的疾病靶点，将药物靶点和疾病靶点取交集，利用Cytoscape软件构建“成分–靶点”网络。采用String数据库构建蛋白互作网络，借助Omicsbean软件及KEGG数据库进行基因本体（gene ontology，GO）功能富集分析及信号通路分析。通过过氧化氢（H₂O₂）诱导的H9c2心肌细胞氧化应激损伤模型，对关键成分进行活性验证。结果 筛选出19个化合物的110个疾病靶点，经分析网络拓扑参数获得14个关键靶点：GAPDH、TNF、EGFR、MMP9、PTGS2、ACHE、REN、PPARG、F2、HSP90AA1、MMP2、IL2、HMOX1、FGF2，通过参与调节PI3K-Akt、血小板活化、肾素血管紧张素系统、细胞凋亡、肿瘤坏死因子、花生四烯酸代谢、钙离子等信号通路来发挥治疗冠心病及稳定型心绞痛的作用。结论 瓜蒌皮注射液主要通过抗炎、保护血管内皮、调节氧化应激、干预肾素血管紧张素系统、调节能量代谢等途径发挥对冠心病及稳定型心绞痛的治疗作用。

Objective Explored the network regulation mechanism of Gualoupi Injection for the treatment of coronary heart disease and stable angina pectoris using network pharmacology. Methods Based on the selection principle of main components and main structural types, 19 compounds of Gualoupi Injection were determined as the research object. The potential targets of compounds were predicted through Swiss Target Prediction and TCMSP databases. The disease targets of coronary heart disease and stable angina pectoris were collected through GeneCards, DisGeNET, and OMIM databases. The drug targets and disease targets were intersected, and the "component- target" network was constructed by Cytoscape software. The protein-protein interaction network was constructed using string database, and the gene ontology (GO) function enrichment analysis and signal pathway analysis were carried out with the help of Omicsbean software and KEGG database. The activity of key components was verified by the H₂O₂-induced H9c2 cells injury model. Results 110 Disease targets of 19 compounds were screened, and 14 key targets including APDH, TNF, EGFR, MMP9, PTGS2, ACHE, REN, PPARG, F2, HSP90AA1, MMP2, IL-2, HMOX1, and FGF2 were obtained by analyzing the network topology parameters, which play a role in the treatment of coronary heart disease and stable angina pectoris by participating in the regulation of PI3K-Akt signaling pathway, platelet activation, renin-angiotensin system, apoptosis, TNF signaling pathway, and arachidonic acid metabolism, calcium signaling pathway and other signaling pathways. Conclusion Gualoupi Injection plays a therapeutic role on coronary heart disease and stable angina pectoris mainly through anti-inflammatory, protecting vascular endothelium, regulating oxidative stress, intervening renin angiotensin system and regulating energy metabolism.

R285

天津市科技计划项目（20KPHDRC00020）