目的：应用系统生物学方法计算机模拟分析丹参与三七配伍协同的分子机制。方法：采用TCMGeneDIT数据库系统，文本挖掘丹参、三七各自所能影响的基因或蛋白质数据；从多个分子相互作用数据库以及文献中查询与这些基因或蛋白质相互作用蛋白质的信息，构建丹参、三七及其配伍后的蛋白质相互作用网络，以Cytoscape软件进行可视化；应用Merge程序比较3个网络的异同；采用IPCA软件分析网络中的高连接区，BiNGO计算机工具进行基因本位论的聚类分析。结果：21个蛋白质与三七和41个与丹参相关，其中9个相同,去除冗余有53个基因应与两药配伍后药理机制相关；构建的3个网络均由数百上千个蛋白质参与组成；丹参、三七相关网络相同蛋白质构成的子网络明显多于直接用重叠基因相互作用信息建立的网络（651:572），模拟配伍后网络与三七、丹参相关网络比较，出现了一个由480新蛋白质相互作用构成的子网络；在丹参、三七相关网络相同蛋白质构成的子网络中，存在4高连接区，基因本位论注释均主要与凋亡、增殖的细胞进程有关，模拟配伍后出现的新子网络功能主要与小G蛋白信号转导通路有关。结论：本研究方法可以更全面模拟药物作用机制，且能模拟分析系统的涌现性；丹参和三七配伍可能主要在凋亡、增殖等以及小G蛋白信号转导通路上发挥协同作用而有效治疗冠心病。

This work adopted systems biology approaches to predict the functional networks for the synergistic mechanisms of the Salvia miltiorrhiza and Panax notoginseng combination. For text mining, TCMGeneDIT was used to retrieve association information regarding genes, Salvia miltiorrhiza and Panax notoginseng; protein-protein interaction information for these genes from databases and Literature data was searched and visualized using Cytoscape; differences between networks were identified by Merge program; highly-connected regions were detected by the IPCA algorithm to infer the significant complexes or pathways in this network; the most relevant functions and pathways were extracted from subnetworks by BiNGO tool. 21 and 41 genes were found to respectively associate with Salvia miltiorrhiza and Panax notoginseng, including 9 genes overlapping both drugs, indicating that 53 genes are associated with drug combination. Protein-protein interaction networks comprised hundreds to thousands of proteins. The subnetworks made up of overlapping proteins between Salvia miltiorrhiza and Panax notoginseng networks were more than the subnetworks reconstituted by protein-protein interaction information concerning the 9 overlapping genes. A new subnetwork emerged by the network about drug combination removed the Salvia miltiorrhiza and Panax notoginseng networks. The most relevant functions and pathways extracted from 4 highly-connected regions in the subnetworks were related to apoptosis, proliferation and small G protein signaling pathways. Taken together, the protocol developed in this study may lead to a deeper understanding of a system as a whole in the mechanism of drug combination and help analyze emergence in a system; Salvia miltiorrhiza and Panax notoginseng combination may have synergistic effects against coronary heart disease in terms of apoptosis, proliferation and small G protein signaling pathways.

中国博士后基金委员会博士后培养项目（200904500425）：类风湿性关节炎寒湿阻络方证相关的系统生物学研究，负责人：陈杲；科学技术部国家创新方法学专项项目（2008IM020900）：中医药科学方法总论研究，负责人：吕爱平；国家自然科学基金委员会青年科学基金项目（30902003）：基于生物网络构建技术探索中药寒热属性的科学基础，负责人：姜淼。