胡芦巴二苯乙烯类化合物改善胰岛素抵抗作用及线粒体调控机制研究

项目名称： 胡芦巴二苯乙烯类化合物改善胰岛素抵抗作用及线粒体调控机制研究

项目编号： No.31470426

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 王洪伦

作者单位： 中国科学院西北高原生物研究所

项目金额： 80万元

中文摘要： 胡芦巴为药食两用资源，具有明确的降血糖作用，但其活性物质基础和生物学机制仍未阐明。近年发现，线粒体结构功能紊乱是糖尿病氧化应激、胰岛素抵抗和β细胞凋亡的共同病理基础，维护线粒体稳态已成为糖尿病防治新策略。课题组前期研究发现胡芦巴种子富含二苯乙烯类化合物，能够显著改善糖尿病小鼠线粒体功能，抑制游离线粒体的氧化损伤，促进胰岛素抵抗脂肪细胞的葡萄糖消耗，降低糖尿病小鼠血糖。本项目利用现代色谱分离方法从胡芦巴制备得到多种二苯乙烯类单体化合物，采用游离线粒体、体外培养肌细胞、肝细胞和脂肪细胞及2型糖尿病大鼠模型，研究二苯乙烯类化合物改善胰岛素抵抗的作用及构效关系；进一步采用RT-PCR、Western blotting和流式细胞术等检测手段，从促进线粒体生物发生，维护线粒体稳态和改善线粒体功能的角度研究二苯乙烯类化合物作用机制。本研究结果将为二苯乙烯类化合物用于2型糖尿病防治提供新的思路。

中文关键词： 胡芦巴；二苯乙烯化合物；胰岛素抵抗；线粒体调控；构效关系

英文摘要： Fenugreek (Trigonella foenum-graecum L.) is a traditional Chinese medicine which were used as a food and drug. Traditional Chinese medicine clinical and modern pharmacological studies have shown that fenugreek exhibit significant hypoglycemic effects while the active components responsible for the blood glucose lowering property are still not sure and the mechanism of action are not clear. Some pathological changes associated with type 2 diabetes, such as oxidative stress, insulin resistance, and βcell disorders were all caused by mitochondrial dysfunction, therefore, the regulation of mitochondrial function is expected to become a potential therapeutic targets of type 2 diabetes. Our previous work have proved that the traditional herb Fenugreek seeds contain a variety of stilbene compounds, which could significantly protect the oxidative damage of mitochondria, promote the Sugar consumption and reduce the accumulation of adipose cell, meanwhile, these stilbene compounds obviously improve the symptom of the diabetic mice. In this project，we separated and prepared some kinds of stilbene compounds，and employ molecular biology techniques and detection methods, for example, RT-PCR, Western blotting and Flow cytometry, and carry out the insulin resistance experiment to determine the structure-activity relationship of these compounds to improve insulin resistance, and to clarify the mechanism of improvement mitochondrial function of these compounds. This study will provide new ideas and scientific basis for the prevention and control of type 2 diabetes mellitus. It is of great significance for finding new dietary treatment strategies and effective molecular targets.

英文关键词： Trigonella foenum-graecum;Stilbene Analogs;Insulin resistance;Mitochondrial regulation;Structure-activity Relationship