沙棘果汁与其活性成分对高胆固醇血症人群的影响及细胞胆固醇代谢机制研究

项目名称： 沙棘果汁与其活性成分对高胆固醇血症人群的影响及细胞胆固醇代谢机制研究

项目编号： No.81472969

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： 王培玉

作者单位： 北京大学

项目金额： 85万元

中文摘要： 心脑血管疾病是人类主要死因之一，血脂异常是其重要危险因素，合理营养有益控制血脂异常，降低发病风险。沙棘果汁含丰富的黄酮（如异鼠李素）、多酚类物质，动物实验证实其降血脂、抗动脉粥样硬化、抗炎等作用；但缺乏对血脂异常人群的干预实验，也缺乏沙棘在人体内吸收、分布及代谢研究。为探究沙棘及其活性成分的降脂作用及机制，本课题拟招募符合标准的高胆固醇血症人群120人，随机分成2组，分别给予沙棘果汁、安慰剂果汁，90天后分析血液、尿液、粪便中沙棘活性成分的代谢转归，以代谢组学方法探讨沙棘及活性成分的降脂作用，同时研究沙棘对血脂相关的CCAAT增强子结合蛋白β及VCAM、ICAM等粘附因子表达的影响.以细胞实验研究沙棘黄酮-异鼠李素对肝脏细胞等胆固醇代谢信号转导通路（LXR-PPARs-ABCA1）等的影响，探讨沙棘及活性成分影响血脂的分子机制，为沙棘预防/辅助治疗心脑血管疾病提科学依据

中文关键词： 沙棘果；异鼠李素；高胆固醇血症；血脂异常；代谢组学

英文摘要： Cardio-cerebral vascular diseases are one of the leading causes of death, and dyslipidemia is an important risk factor of it. Adequate nutrition is beneficial for improving dyslipidemia as well as lowering the risk of cardio-cerebral vascular diseases. Sea-buckthorn fruit is rich in flavonoids (isorhamnetin) and polyphenols which have been verified in animal experiments to have effects of reducing blood lipids, anti-atherosis and anti-inflammation. However, intervention study using sea-buckthorn for the people with dyslipidemia and mechanism research were not reported. The absorption, distribution and metabolism of sea-buckthorn in the human body was not clear. To investigate the function of sea-buck thorn on plasma cholesterol and its mechanism, 120 subjects with meeting a criterion of hypercholesteremia will be recruited, and randomly divided into two groups. The subjects will be given sea-buckthorn fruit juice and placebo juice, respectively. After 90 days intervention, the metabolites and pharmacokinetics of active ingredients of sea-buckthorn in the blood, urine and faeces of the subjects will be analyzed. The effects of sea-buckthorn and its ingredients on plasma cholesterol, on the expression of blood lipids related CCAAT enhancer binding protein β(C/EBP-β), and adherence factors of VCAM, ICAM will be investigated with metabonomics. In order to clarify the cholesterol-lowering mechanism of the sea-buckthorn, the effects of sea-buckthorn's active ingredients, flavonoids-isorhamnetin on cholesterol metabolism in hepatocyte and on the genetic signal transduction (LXR-PPARs-ABCA1) will be explored using in vitro experiment. This study is aimed at providing an evidence for whether sea-buckthorn can be used for preventing or adjuvant curing the dyslipidemia and cardio-cerebral vascular diseases.

英文关键词： sea-buckthorn;Isorhamnetin;hypercholesteromia;dysliperdemia;metabonomics