灵芝孢子粉多糖抑制肥胖所诱导的炎症和胰岛素抵抗的作用机制研究

项目名称： 灵芝孢子粉多糖抑制肥胖所诱导的炎症和胰岛素抵抗的作用机制研究

项目编号： No.81473397

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： 王兴亚

作者单位： 浙江中医药大学

项目金额： 75万元

中文摘要： 肥胖所诱导的慢性炎症在胰岛素抵抗和糖尿病发生发展中起重要作用机制的理论已被广泛接受。由于缺乏对这一机制的认识，近几年来灵芝多糖在防治胰岛素抵抗以及糖尿病发生发展方面的研究陷入瓶颈阶段。本课题拟突破传统降糖评价方法和作用机制方面的研究局限性，从建立模型为出发点，研究最接近人类II型糖尿病胰岛素抵抗的Agouti Ay炎性肥胖糖尿病小鼠以及高脂饲料所诱导的炎性C57/BL6胰岛素抵抗小鼠，重新评价灵芝多糖抑制炎症反应、调节糖代谢和胰岛素抵抗的作用与机制。拟通过体外炎症诱导实验，在细胞水平上进一步验证灵芝多糖抑制巨噬细胞浸润、NLPR3炎症小体的表达与活性、以及炎症因子分泌的作用。还将利用基因敲除技术在体内外研究NAG-1基因在灵芝多糖调控以上反应中的重要作用。并基于此机制探讨灵芝多糖抗炎提高胰岛素敏感性所涉及的信号传导通路。本研究将为中医药在通过抗炎来提高胰岛素抵抗与糖尿病防治上提供新靶点。

中文关键词： 灵芝多糖；巨噬细胞；胰岛素抵抗；炎症小体；NAG-1

英文摘要： Obesity-induced chronic inflammation is one of the key mechanisms of insulin resistance and type II diabetes. Due to the lack of acknowledgement of this concept, the study of the effects of the polysaccharide of Ganoderma Lucidum Spores (PGLS) on improving insulin sensitivity and inhibiting the development of type II diabetes has been stuck. This proposal will overcome the limitation of traditional methods and inappropriate mechanism. Through establishing study models, re-evaluate the effects and mechanism of PGLS to inhibit inflammation, regulate glucose homeostasis, and insulin resistance using the Agouti Ay mouse model and HFD-induced inflammatory mouse models, which most resemble human type II diabetes and insulin resistance. Through in vitro induction of inflammation, we would further determine whether PGLS could inhibit macrophage infiltration, NRLP3 inflammasome activity, and the secretion of inflammatory cytokines at cellular levels. We will also use siRNA or knockout techniques to determine the important role of NAG-1 in the above effects of PGLS both in vivo and in vitro. In addition, we will study the potential signal transduction pathways that are involved in the inhibition of insulin resistance by PGLS. Our proposal will provide new therapeutic target for the improvement of insulin sensitivity and treatment of type II diabetes by Traditional Chinese Medicine.

英文关键词： polysaccharide;Macrophage;Insulin Resistance;inflammasome;NAG-1