注射用丹参多酚酸盐联合阿司匹林治疗稳定型心绞痛机制的生物分子网络研究

Mechanism of Salvianolate injection combined with aspirin in treatment of stable angina pectoris based on biomolecules network

该研究运用生物分子网络分析方法,预测注射用丹参多酚酸盐与阿司匹林联合用药治疗稳定型心绞痛的作用机制。从Genecards,STITCH,Dis Ge NET数据库获取注射用丹参多酚酸盐、阿司匹林及稳定型心绞痛(stable angina pectoris,SAP)的相关基因;采用Agilent Literature Search文献搜索软件构建生物分子网络;经AP,MCODE和MCL 3种方法对生物网络进行模块识别;通过DAVID软件进行相关KEGG通路识别。结果表明注射用丹参多酚酸盐和阿司匹林对SAP分子网络的覆盖率分别为45.92%,62.56%,联合用药的覆盖率为71.64%。注射用丹参多酚酸盐、阿司匹林与SAP前10个重要节点中,MAPK14,MAPK8,IL-6,IL-8为2个药物共同重叠的SAP重要节点,AKT1和IFNG为注射用丹参多酚酸盐单独重叠的SAP重要节点,EPHB2和TP53为阿司匹林单独重叠的SAP重要节点。2个药物共同参与的SAP相关信号通路包括JAK-STAT信号通路和MAPK信号通路等;注射用丹参多酚酸盐单独参与的SAP相关信号通路包括VEGF信号通路和1型糖尿病信号通路;阿司匹林单独参与的SAP相关信号通路包括AA代谢、亚油酸代谢信号通路等。该研究表明联合用药一方面在抗炎症反应和抑制动脉粥样硬化发展方面有疗效增强作用;另一方面注射用丹参多酚酸盐在阿司匹林抗血小板聚集的基础上能够保护血管内细胞和调节糖代谢,起到疗效相加作用。

Biomolecular network analysis was used to predict the mechanism of Salvianolate injection combined with aspirin for the treatment of stable angina pectoris（SAP）. Related genes of Salvianolate injection, aspirin and SAP were obtained from Genecards, STITCH and DisGeNET databases. Agilent literature search software was used to construct biomolecular network; modules were identi- fied by AP, MCODE and MCL methods. DAVID software was used for identification of related KEGG pathways. Results showed that Salvianolate injection and aspirin had a coverage rate of 45.92% , 62.56% respectively for SAP molecular network, and the coverage rate was 71.64% in combined use. The top l0 important nodes of SAP overlapped with Salvianolate injection and aspirin included MAPK14, MAPKS, IL-6 and IL-8. The important SAP nodes overlapped with Salvianolate injection alone included AKT1 and IFNG, and the important SAP nodes overlapped with aspirin included EPHB2 and TP53. Related SAP signaling pathways with combined Salvianolate injection and aspirin included Jak-STAT signaling pathway and MAPK signaling pathway. Related SAP signaling pathways with Salvianolate injection alone included VEGF signaling pathway and type 1 diabetes signaling pathway. Related SAP signaling path-ways with aspirin alone included AA metabolism, linoleic acid metabolism signaling pathway, etc. The results showed that Salvianolate injection and aspirin combination had an enhancement effect in treatment of SAP through anti-inflammatory reaction and inhibition of atherosclerosis development; in addition, the combination use may have an additive effect through the antiplatelet aggregation, protec- ting endothelial cells, regulating blood lipid and regulating glucose metabolism.