动态网络模块分析丹酚酸B治疗冠心病作用机制

Mechanism of salvianolic acid B treating coronary artery disease based on dynamic network modules

丹酚酸B是丹参治疗冠心病的主要活性成分之一,具有良好的防治冠心病疗效.通过数据库检索及药效团筛选确定了丹酚酸B的作用靶点,根据靶点蛋白相互作用信息构建其静态蛋白相互作用网络,并整合冠心病表达谱构建疾病和正常状态下的共表达蛋白相互作用网络.采用基于边聚类的快速模块识别算法FAG-EC对疾病状态的共表达网络进行模块分析和GO富集分析,然后将获得的功能模块映射到正常状态下的共表达网络,获得相对应的功能模块,并对不同状态下的功能模块进行对比分析,揭示模块在不同状态下动态变化信息;基于模块功能分析,结果显示,丹酚酸B主要通过调节免疫/炎症反应、凝血、血液循环、花生四烯酸代谢、成纤维细胞生长因子受体信号传导途径、肾素-血管紧张素系统、脂质代谢以及基础代谢等途径达到治疗冠心病的效果.

Salvianolic acid B（Sal B） is one of the main active components of Salvia miltiorrhiza, which has good effect on treating coronary artery disease（CAD）. However, the mechanism of Sal B treating the CAD has not been illuminated clearly. Therefore, the construction and analysis of dynamic network modules was used to elucidate the mechanism, which has the advantage of revealing the dynamics of protein interaction network in the paper. Firstly, the targets＇ information of Sal B was obtained from pharmacophore screening and database searching（STITCH CHEMBL）. Secondly, the protein-protein interaction（PPI） of targets was achieved from STRING, and the protein interaction network（PIN）, also called the static PIN, was constructed by Cytoscape. Then, the co-expression PIN（Ce PIN） was constructed by integrating the static PIN with the gene expression profile of CAD from GEO which contains normal and disease condition samples. The Co-PIN consists of co-expression PPIs which are significantly expressed PPIs in the CAD gene expression profile. Next, the modules of Ce PIN in disease condition were analyzed based on FAG-EC and GO enrichment. Finally, the modules in disease condition were mapped to the normal condition, and the comparative analysis of modules in different condition revealed the dynamic information of different biological condition. Meanwhile, based on the analysis of the modules in disease condition, the mechanism of Sal B treating CAD was related to the regulation of immune/inflammation response, coagulation, blood circulation, arachidonic acid metabolism, fibroblast growth factor receptor signaling pathway, the renin-angiotensin system, lipid metabolism and basic metabolism.