基于LXRβ拮抗机制的桑白皮有效成分降糖降脂的分子机制

项目名称： 基于LXRβ拮抗机制的桑白皮有效成分降糖降脂的分子机制

项目编号： No.81473392

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： 杨柏灿

作者单位： 上海中医药大学

项目金额： 72万元

中文摘要： 肥胖及其伴随的高血脂症、糖尿病和心血管疾病等为严重的全球性问题，每年引起约300万人死亡。核受体为治疗肥胖等代谢性疾病重要靶点。最近的研究表明，LXR拮抗剂对治疗肥胖、高脂血症、动脉粥样硬化等代谢性疾病的有良好应用前景。我们的研究发现桑白皮提取物含有LXRβ选择性拮抗剂，并对小鼠肥胖、高脂血症和高血糖等具有治疗作用。本项目拟在现有工作的基础上，观察桑白皮提取物及化合物桑色素对高脂诱导的肥胖小鼠、db/db小鼠和LDLR突变小鼠体重、血脂、胰岛素抵抗和动脉粥样硬化斑块形成的作用，明确桑白皮及其化合物对代谢性疾病的治疗作用。进一步使用报告基因分析技术和TR-FRET共活化因子分析技术研究桑色素对LXRβ的特异性结合，并使用LXRβ突变小鼠验证其作用靶点，明确桑白皮的有效成分，揭示其降脂减肥的作用机制，为开发降脂减肥的桑白皮有效成分提供实验依据。其结果对中医药研究具有重要的理论意义和应用价值。

中文关键词： LXRβ；桑白皮；降糖降脂；分子机制

英文摘要： Obesity and related hyperlipidemia, type II diabetes and cardiovascular diseases are world wide problems, which cause 3 million of death each year. So far there is no effective anti-obesity drug on the market. Nuclear receptor transcription factors are useful drug targets for metabolic diseases. Recent studies have shown that LXR antagonist has therapeutic roles in obesity, hyperlipidemia, atherosclerosis（AS) and other metabolic diseases. Our preliminary data revealed that Morus alba contains selective LXRβ antagonist and has therapeutic effects on obesity, insulin resistance and hyperlipidemia in the mice. The present project will observe the effects of Morus alba and its components on, hyperlipidemia, insulin resistance and AS in the high-fat diet-induced obese mouse, db/db mouse and LDLR-/- mice. Furthermore we will use the reporter assay to analyze which morin is the selective LXRβ antagonist, and use the LXRβ-/- mouse to confirm the mechanism based on the regulation of LXRβ signaling. The data will verify the effective compound of Morus alba on the therapy of obesity, hyperlipidemia and AS, and will elucidate its mechanism. Our study will provide the experimental evidence for the development of Morus alba derived compounds as the therapy for obesity, hyperlipidemia and AS.

英文关键词： LXRβ;cortex mori radicis;reduce blood glucose and lipid;molecular mechanism