高脂血症发病呈逐年升高，其中高胆固醇血症是形成冠状动脉粥样硬化性心脏病和中风的主要危险因素。我们的前期研究发现，海棠果提取物可显著降低高脂饲料诱导的小鼠血清高胆固醇和低密度脂蛋白，增加肝脏的胆固醇7α羟化酶（CYP7A1）mRNA和蛋白含量。为研究海棠果降胆固醇的活性部位，及是否通过作用于核受体调控CYP7A1基因表达发挥作用，本课题拟进一步建立海棠果质量标准，分离海棠果总多糖和总多酚，并考察其降胆固醇的药效学，明确海棠果降胆固醇的活性部位，同时研究海棠果是否有防治LDLR基因敲除小鼠动脉粥样硬化的作用。对已知海棠果主要成分进行报告基因分析，发现可能影响LXRα或FXR调控CYP7A1基因表达的活性成分，最后使用CYP7A1基因敲除小鼠验证其作用机制，以揭示海棠果降胆固醇的有效成分，并阐明其分子机制，为开发具有我国自主知识产权的降总胆固醇中药新药提供实验依据。

Hyperlipidemia is a metabolic disease with rapidly increasing prevalence. Hypercholesterolemia is a major risk for atherosclerosis and relevant cardiovascular disease and stroke. In our preliminary study, we found that extracts of crabapples could lower serum total cholesterol and low-density lipoprotein cholesterol, and increase the mRNA and protein levels of cholesterol 7α- hydroxylase (CYP7A1) in the liver tissue of high-fat diet-induced obese mice. To reveal which components in crabapples play cholesterol-lowering effect, and its underlining mechanism, we will separate polysaccharides and polyphenols from crabapples, and test the therapeutic effects of the components. We also will use LDLR-/- mouse model to analyze whether the crabapples have preventive or therapeutic effects on plaque formation of atherosclerosis. Using reporter assay, we will test the constituents from crabapple for their regulation on CYP7A1 transcription activity of nuclear receptor transcription factor LXRα and FXR to find the active compounds. Finally we will use CYP7A1 knockout mice to verify the mechanism. Our study will shed lights on the cholesterol-lowering mechanism of crabapple, and will provide the experimental basis for the development of new drug or nutraceuticals.