中文摘要
为了从分子和细胞层面快速揭示中药效应产生的生物途径,发现不同效应之间的因果关系以及中药效应在细胞之间的传递关系,本项目在整合基因调控网络、细胞信号通路、代谢网络的基础上,以基因、蛋白质的细胞特异性表达数据为依据,通过赋予节点连通率参数、效度参数和增益系数,赋予边流率参数、流度参数和增益系数,建立细胞特异性网络。以细胞间信号分子与其受体的对应关系,通过对细胞特异性网络的输入、输出形式化建模,实现了对组织、器官和系统的多细胞耦合关系分析,建立用于解析中药作用效应跨细胞传递机制的细胞耦合地图。最后,以四物汤中各单味药及复方为例,分别利用细胞特异性网络和细胞耦合地图解析四物汤中各单味药及复方对乳腺癌细胞及乳腺组织的作用机理,验证细胞耦合地图用于中药作用机理解析的可行性。研制基于细胞耦合地图的中药作用机理辅助解析软件平台,为阐释中药炮制、药性、配伍原理提供基础。
英文摘要
To reveal the mechanism of traditional Chinese Medicine (TCM) and find the cause-result relationship of different effect, this project integrate gene regulation networks, signaling pathways and metabolic networks. Using the cell-type specific expression data of genes and proteins as the sources, through defining the linkage rate, effect degree and gain coefficient for nodes and defining the flow rate, flow degree and gain coefficient for edges, establish the cell specific networks. Through formalizing the cell-specific network using input-output pattern, establish cell-cell coupling map of the multi-cell tissues, organs and systems. Lastly, the mechanism and effects of SI-WU-decoction on breast cancer cells and normal breast cells would be deciphered based on the single cell strategy and multi-cell strategy, respectively, for validating the results obtained from cell-cell coupling model. Software aided the mechanism elucidation will be established. Results of this project would be important to reveal the scientific principles of TCM theory on preparation, natures and compatibility.
