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

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.

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

心血管疾病是人类的主要死因之一，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，为探究沙棘及其活性成分的降脂作用及机制，本课题招募符合标准的高胆固醇血症人群111人，随机分成2组，沙棘果汁组56人，安慰剂组55人，分别给予沙棘果汁、安慰剂果汁。经过90天干预，试验组53人、对照组44人完成实验，并获得血液、尿液、粪便样本进行分析研究。.通过对实验0天、45天、90天血液样本中血脂进行检测，结果显示沙棘对高胆固醇血症患者TC、LDL-C、HDL-C干预效果不显著TG在两组中均呈上升趋势，推测可能是由于沙棘中所含果糖等成分导致。通过对血清中炎症标志物hsCRP的检测发现，与对照组相比，沙棘组在整个干预过程中呈现出明显的下降趋势，提示沙棘果汁可能具有一定的抗炎效果。但对VCAM、ICAM等粘附因子表达无显著影响。通过对受试者进行身体测量发现，12周的干预后，两组间受试者BMI与基线相比无显著差异，两组受试者收缩压及体脂率均呈现出总体的下降趋势。与对照组相比，沙棘果汁组舒张压在为期90天的干预过程中呈现出明显的连续的下降趋势，但两组间无显著统计学差异，提示沙棘果汁可能存在潜在的降血压作用。.采用NMR对沙棘试验组45名受试者0、45、90天的血浆样本进行监测分析，结果显示脂质合成代谢呈现先升后降的趋势。干预期间糖酵解和柠檬酸循环无明显改变。然而，45d时血糖水平升高，90d时血糖水平较0d有所改善，这可能与葡萄糖原氨基酸的变化有关。干预期间肠道微生物群发生的变化需要进一步分析.细胞实验研究发现不同浓度异鼠李素对胆固醇、Ox-LDL负荷后肝脏HepG2细胞的LXRα蛋白表达存在显著影响，并且存在剂量反应关系，但是未发现对SREBP-2、ABCA1蛋白的影响，推测异鼠李素可能通过影响LXRα通路来影响宿主的脂代谢；且在RNA水平也存在显著影响，但剂量反应不明显，同时还发现ABCA1mRNA、miR-33在转录水平上没见显著改变，进而推测异鼠李素在RNA和蛋白水平均能影响LXRα代谢通路。