长期高脂饮食可导致动脉粥样硬化（AS），AS病程和清道夫受体（SR）摄取血清氧化修饰低密度脂蛋白（ox-LDL）的能力密切相关，而LDL脂质微环境的变化可以早期预警ox-LDL形成。项目前期已确证了降脂活性较好的苦丁茶皂苷能显著上调高脂动物肝脏中SR的表达。本项目将整合应用LC-QTRAP-MS/MS和LC-QTOF-MS/MS技术，建立基于LC-QTRAP-MRM模式的特征谱群分析方法，用于定性和定量分析血清LDL脂质微环境在金黄地鼠AS病程中的动态变化，筛选微环境中能够反映ox-LDL产生的早期生物标志物。同时结合SR相关基因和蛋白的差异性表达情况，利用上述方法评价苦丁茶皂苷对金黄地鼠AS病程中血清LDL脂质微环境的改善作用，明确其预防AS的药效及作用机制。本项目研究成果将为苦丁茶预防AS提供新的科学依据，并从改善LDL脂质微环境的角度为防治AS疾病中药的研究提供了一个新的科学视角。

Long-term high-fat diet can lead to the formation of atherosclerosis (AS). The occurrence and development of AS is closely related to the ability of scavenger receptors on the cell-surface to absorbed oxidative modification of serum low-density lipoprotein (ox-LDL). The changes of lipid microenvironment can also reflect the degree of oxidation in serum low-density lipoprotein. The effects of Ilex kudingcha on lipid metabolic disorder have been reported in our previous study, and a group of saponins can significantly up-regulated the expression of SR-AI, SR-BI and CD36 in liver of hyperlipidemic animals. On the base of our previous work, the project plans to strategically combine LC-QTRAP-MS/MS and LC-QTOF-MS/MS to establish an analytical method, named “characteristic profiling groups” of LC-QTRAP-MRM, to investigate the small molecular lipid composition on the serum LDL. The established strategy can be used of qualitative and quantitative analysis of lipid composition in serum LDL of golden hamster during the course of AS. And thus the early biomarkers will be screened and identified to reflect the occurrence of ox-LDL. Combined with results of the gene and protein expression of scavenger receptors in liver, a dynamic study will be performed to clarify the effect and mechanism of preventive intervention of saponins from Ilex kudingcha on the lipid microenvironment of serum LDL in the course of AS. The results of the study will provide novel evidence of saponins from Ilex kudingcha in the prevention of AS, and also provide new insights in the study of preventive medicine on AS from the point of intervention on lipid microenvironment of serum LDL.