苦丁茶冬青药效分子群多途径改善动脉粥样硬化的分子机制研究

动脉粥样硬化是引起冠心病和脑中风等心脑血管疾病的主要因素，严重危害人类健康。寻找调血脂、抗动脉粥样硬化药物，一直是全球药物研究热点。苦丁茶冬青叶是传统中药和保健饮品苦丁茶的正品来源，具有确切的降血脂和抗动脉粥样硬化作用，但其作用机制尚不明确。本课题在前期发现苦丁茶冬青总皂苷具有明显的降血脂和抗动脉粥样硬化作用，并对其机制进行初步探讨的基础上，拟采用高脂饲料诱导的ApoE-/-小鼠高血脂和动脉粥样硬化模型，结合体外细胞模型，从肠腔脂质转运、巨噬细胞内胆固醇蓄积和内皮细胞功能等方面，系统阐明苦丁茶冬青药效分子群对动脉粥样硬化各相关通路的调控作用及其分子机制，构建其药效分子群的调控网络。项目实施，不仅能够有效地提升苦丁茶抗动脉粥样硬化功效的科学认识，而且也为多成分、多途径、多靶点抗动脉粥样硬化药物的发现提供新的思路，具有重要的理论意义和潜在的临床价值。

Atherosclerosis is a major factor in causing coronary heart disease, stroke and other cardio-cerebrovascular diseases, which are seriously harmful to human health. Seeking and development of drugs against atherosclerosis has been a research focus. The leaves of Ilex kudingcha C. J. Tseng is the authentic source of traditional Chinese medicine and health beverages, which has great hypolipidemic and anti-atherosclerotic effects. However, the underlying mechanisms of anti-atherosclerosis of Ilex kudingcha remain unclear. Previous studies have showed that Ilex kudingcha total triterpenoid saponins extract decreased the levels of serum total cholesterol, triglyceride and inhibited the atherosclerotic plaque formation in the artery on ApoE-/- mice. Based on the preliminary pharmacological activities of Ilex kudingcha, this project will investigate the pathways and molecular mechanisms of therapeutric ingredient composition of Ilex kudingcha against atherosclerosis in terms of small intestinal lipid absorption, macrophages endocytic effect, and endothelial cells function by using high fat induced ApoE-/- mice and cell models. The results of this study will make a comprehensive understanding of the role of Ilex kudingcha in the pharmacological mechanism of anti-atherosclerosis, and provide new ideas on drugs discovery by multi-component, multi-pathways, and multi-target action mechanisms against atherosclerosis. Our findings will be of great theoretic significance and potential clinical value.