中文摘要
青黄散作为一种治疗慢性粒细胞白血病的有效中药方剂,有较好的临床和实验基础,但传统药理学单一靶点的疾病机理的认识观念和药物研究方法已不能适应由多基因、多功能蛋白相互作用紊乱而形成的疾病,同样不适宜中药复杂作用机制研究。而阐释中药复杂化学体系与病证复杂系统的相互作用是目前中医药研究的重点和难点。.随着系统生物学的发展,网络药理学和分子对接技术为探索中药有效成分协同干预疾病的内在原理和构建中医多靶点精准治疗模式提供了可行的研究策略。.与传统实验设计不同,本课题在前期研究的基础上,拟采用蛋白质相互作用网络分析方法对慢粒网络关键靶点进行预测,同时采取计算机辅助药物设计方法将青黄散中的分子复合物与慢粒关键蛋白进行分子对接,优化筛选对接靶点;并通过基因转染技术分别建立的细胞模型和青黄散肠道吸收液模型,进行一系列的体外药理活性评价及验证,以期从系统生物学角度揭示中药抗肿瘤的多靶点干预机制。
英文摘要
Qing Huang Powder, a kind of effective traditional Chinese medicine prescription for the treatment of chronic myelocytic leukemia, has a good foundation in clinical and experimental research. However, the pharmaceutical research methods of the single target in traditional pharmacology can not have a good explaination to the pathogenesis of diseases which caused by multiple gene and multifunctional protein interaction disorder and the mechanism of action of TCM compound recipe. It is also not suitable for Chinese traditional medicine complex mechanism research. Besides, to interpret the interaction between traditional Chinese medicine complex chemical system and disease complex system is the emphasis and difficulty in the current research of traditional Chinese medicine.. With the development of systems biology, network pharmacology and molecular docking technology provide a feasible research strategy on the exploration for the intrinsic principle of TCM effect on diseases and the foundation of TCM multiple targets accurate treatment mode. . Contrast to traditional experiment, on the basis of our previous studies, we are going to predict the network key targets for CML by protein interaction network analysis method, and perform molecular docking between the molecular compounds of Qing Huang Powder and the key protein of CML using computer aided drug design method, then optimize and formulate docking targets; Besides, we'll establish cell model and Qing Huang Powder intestinal absorption model respectively by gene transfection technology, next, evaluate and validate pharmacological activities in vitro in order to reveal the anti-tumor mechanism of multiple targets of TCM from the view point of system biology.
