活血化瘀抗动脉粥样硬化与血栓形成的剪应力效应机理

项目名称： 活血化瘀抗动脉粥样硬化与血栓形成的剪应力效应机理

项目编号： No.81473548

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 廖福龙

作者单位： 中国中医科学院中药研究所

项目金额： 75万元

中文摘要： 课题组近年基于中药药理研究,开拓了一门新的交叉学科--生物力药理学,并在国际药理学权威刊物Trends Pharmaco Sci（2006年IF:13.6）发表,引起国际高度关注。本标书假说如下:从生物效应考虑,血流剪应力可等效为药物,具有确切的调节血管内皮细胞多方面功能的量-效关系,可干预与防治AS及血栓形成等病变。血流剪应力低下是血瘀证的共性特征,适度提高血流剪应力是活血化瘀的重要科学内涵之一。本课题从血管内皮细胞/血流剪应力/血液相互作用入手,进行三个层次的实验研究:一、全程生理剪应力对血管内皮细胞AS、血栓形成及血栓溶解有关因子的剂量-效应关系；二、在离体血管对于细胞层次的结果做进一步研究;三、在整体动物AS与血栓形成模型上研究非药物活血化瘀(运动)与活血化瘀药对(丹参+山楂)的分别贡献与联合效应。本项目探讨活血化瘀防治AS与血栓形成的新途径与机制,并以边缘学科促进中药药理学发展。

中文关键词： 生物力药理学；剪应力；活血化瘀；动脉粥样硬化；血栓形成

英文摘要： Recently, we developed a new borderline discipline-biomechanopharmacology for pharmacology of Chinese medicine. The concept was introduced in the well-known journal--Trends in Pharmacological Sciences (IF: 13.6 in 2006). The article then attracted attention internationally. The hypothesis of the project is the follows: Low shear stress (SS) in blood vessel is a common feature in blood stasis syndrome in Chinese medicine, and one of the intension of the therapeutic principle of activating blood circulation to remove blood stasis (ABCRBS) is to elevate shear stress appropriately. Therefore, the functions of endothelial cells are regulated by the elevated SS, and the preventive and therapeutic effects could be gained for intervention of atherosclerosis (AS) and thrombosis. The project focuses on the interactions among endothelial cells, blood SS and blood. The project consists of three categories of research: Firstly, the dose-response between the factors secreted by endothelial cells related to atherosclerosis, thrombosis and thrombolysis and the multi-levels of full range physiological shear stress. Secondly, the responses of the ex vivo vessel segment under different SS will be explored as a continuation of the first. Based on the factorial design, the joint application of a popular pair of ABCRBS herbs, Salvia miltiorrhiza and Crataegus Pinnatifida, with the measure of elevating shear stress (exercise) will be investigated for prevention and treatment of AS. Animal experiment of AS model combined with thrombosis and injury models in vitro and ex vivo of endothelial cells will be used. Parameters in lipid metabolism, inflammatory factors, anti-oxidation etc will be monitored. Thirdly, animal models of AS and thrombosis will be employed to investigate the effects of non-drug ABCRBS (exercise) and the herbal pair of ABCRBS (Salvia miltiorrhiza +Crataegus Pinnatifida) individually and jointly. The project focuses on the biomechanopharmacological mechanism and new approach in intervention of AS and thrombosis, and the development of the pharmacology of Chinese material medica.

英文关键词： biomechanopharmocology;shear stress;activating blood circulation to remove blood stasisi;atheroscler;thrombosis