基于“血清药物化学—计算机辅助分子预测—药靶蛋白协同”三维模式下青黄散治疗慢粒的配伍机制研究

There is an exactly clinical curative effect of traditional Chinese prescription Qinghuang powder in treatment of chronic myeloid leukemia. The study on the composition of the indigo naturalis and the realgar is gradually revealed with the development of pharmacology. However, the lack of research on the internal molecular mechanisms of the compatibility of the traditional Chinese medicine complex reflects the lag of the modernization of traditional Chinese medicine compatibility system, which is the key point of the current research of Chinese medicine. . In recent years, the emergence of various molecular biotechnology has laid the foundation for the rise of systems biology, the cooperation of biomedical technology also makes it possible to explain the internal mechanism of traditional Chinese medicine compatibility to intervene disease at the molecular level in the context of systematic biology. . On the basis of our previous studies, we are going to use serum pharma-cochemistry to analyse the effective components in blood, which are then used to perform molecular docking and build drug target network with the key target of CML analysis after database mining. The establishment of a three-dimentional Model, “computer aided molecular prediction-high throughput target enrichment technology-synergistic effect network of drug and target protein”, is a bold attempt to reveal the intrinsic mechanism of traditional Chinese medicine in the treatment of tumors from the perspective of systemic biology.

中医古方青黄散临床治疗慢性粒细胞性白血病疗效确切，对单药青黛、雄黄成分的研究随着药理学的发展而逐渐被揭示，但其配伍内在分子机制探究的缺乏映射了目前中医药复杂配伍体系现代化研究的滞后性，是目前中医药研究的重点、难点。. 近年来，各种分子生物技术的涌现为系统生物学的兴起奠定了基础，生物医学技术的衔接也使从分子层面阐释中药配伍干预疾病的内在机制在系统生物学的大背景下成为可能。. 本课题在前期研究基础上，采用血清药物化学分析血行有效成分，将其与数据库挖掘分析后构建出的慢粒关键靶点进行分子对接与药靶网络构建，“计算机辅助分子预测技术、高通量靶标富集技术与药靶蛋白互作网络”的三维模式构建是从系统生物学角度揭示中药协同配伍治疗肿瘤的内在机制的大胆尝试。

摘要：中药药效物质基础是指中药及其复方制剂中发挥药效作用的化学成分，是中医药实现作用的物质基础。但由于中药成分的复杂性以及研究思路和方法等多种因素的制约，中药复方多成分、多靶点、多途径的特点难以被表征。从血清中分离、鉴定移行成分，研究血清中移行成分与传统疗效的相关性，阐明体内直接作用物质的代谢及体内动态情况的血清药物化学提供了新理解。并且，以计算机辅助分子预测技术作为其中的代表性技术，通过结合网络药理学和分子对接技术，从而发现中药药效物质的新药物靶标、发现其协同作用机制，可为中药多靶点抗肿瘤研究提供一条从已知药效成分出发、进行直接多靶点作用机制预测的研究思路。. 本课题通过血清药物化学相关技术筛选、鉴定青黄散有效化学成分、入血成分及代谢产物，确定了一系列青黄散的药效物质基础，进一步通过详实计算与筛选，获得了疾病靶标数据；随后构建了疾病靶标网络、青黄散关键成分网络以及“药-靶”网络，统计学方法筛选出有效的药靶作用对，并且通过分子对接技术进一步阐明作用机制，从结构生物学角度全面、科学的分析青黄散协同配伍干预慢粒的有效机制。