基于靶向垂钓策略探讨广枣抗冠心病药效物质基础及作用机制

冠心病是人类健康的“头号杀手”，现代医学研究表明：PPAR-γ，COX-2 和 ACE 是心血管疾病的重要治疗靶点。广枣是蒙医临床用于治疗心血管疾病，且疗效确切的特色药材，具有抗心律失常，改善心肌缺血等作用，但其治疗冠心病的药效物质基础和作用机制尚不明确。本课题以广枣为研究对象，从动物水平、细胞水平和分子水平，阐明广枣抗冠心病的作用机制。在此基础上，合成功能化多靶点（PPAR-γ，COX-2 和 ACE）亲和磁性微球，以多靶点靶向垂钓捕获广枣中活性成分群，并采用分子对接技术分析受体-配体相互作用，从而全面研究广枣活性成分的化学结构与防治冠心病活性的关联性，从分子水平阐明广枣防治冠心病的药效物质基础和作用机制，为从广枣中寻找防治冠心病的先导化合物奠定坚实基础。

Coronary heart disease (CHD) was considered as the “Number One Killer” for human health, and the modern medicine investigation indicated that PPAR-γ, COX-2 and ACE were the important therapeutic targets of CHD. Choerospondias axillaris shows the therapeutic effects of antiarrhythmic and improving myocardial ischemia and so on, which was applied as the characteristic herbs for the treatment of cardiovascular disease in clinical practice of Mongolian medicine. The current investigation clarified the mechanism of action of Choerospondias axillaris against CHD from the animal level, cell level and molecular level. On the basis, synthesis functionalized multi-targets (PPAR-γ，COX-2 and ACE) affinity magnetic microspheres to targeted fishing the lead compounds with the merits of multi-targets regulating agent in Choerospondias axillaris, and then Molecular docking technology was used to analyze the receptor-ligand interaction, so as to comprehensive study the relationship of chemical structures of actives and prevention of CHD. The aim of this study is to elucidate the substance basis and mechanism of Choerospondias axillaris in preventing and treating CHD from protein level and molecular level, finally reaching the exploration of lead compounds applying for the prevention of CHD.