当归六黄汤免疫调控胰岛素抵抗的作用机制及配伍研究

项目名称： 当归六黄汤免疫调控胰岛素抵抗的作用机制及配伍研究

项目编号： No.81473585

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： 向明

作者单位： 华中科技大学

项目金额： 74万元

中文摘要： 胰岛素抵抗（IR）为糖尿病的主要发病环节，也是慢性炎症。肥胖及脂质代谢异常可促进炎症细胞浸润、细胞因子和脂肪代谢物分泌而降低胰岛素敏感性。最新研究发现肥胖者的内脏脂肪组织聚集表达PPAR-γ的独特调节性T细胞（Tregs），通过抗炎及免疫调节增加胰岛素敏感性，成为IR治疗的潜在靶点。取自《兰室秘藏》的名方当归六黄汤具有治疗糖尿病及其并发症的作用。前期研究发现当归六黄汤既可诱导Tregs，保护T1DM胰岛β细胞，又可改善糖、脂代谢，增加胰岛素敏感性而抗2型糖尿病。为明确其抗IR作用机制及物质基础，我们拟通过IR自发病动物模型确定复方药效及最优配伍；通过内脏脂肪组织炎症细胞与免疫细胞相互作用、Foxp3与PPAR-γ的相互关联以及炎症信号通路和胰岛素抵抗信号通路的分析，探讨复方和配伍的免疫调控代谢作用机制；通过转基因动物及细胞过继转移模型明确当归六黄汤抗IR分子靶点以及治疗糖尿病的配伍科学性。

中文关键词： 当归六黄汤；免疫调控代谢；胰岛素抵抗；2型糖尿病；配伍机制

英文摘要： Insulin resistance (IR) plays a central role in the development of diabetes and is also a low degree of chronic metabolic inflammation.The obesity and abnormal lipids metabolism increase infiltration of inflammatory cells，the secretion of cytokines and lipid metabolites,which cause the decrease in insulin sensitivity. It has been found that the unique regulatory T cells(Tregs) expressing PPAR-γ and recruiting in visceral adipose tissue of obese, could improve insulin sensitivity through anti-inflammation and immunosuppression effects,which makes it to be a potential target of treating IR.Dangguiliuhuang decotion which is from Lan Shi Mi Cang has an effect on diabetes and its complications. Our preliminary study revealed that Dangguiliuhuang decoction could not only induce Treg cells,protect pancreatic β cell and reduce the incidence of T1DM, but also improve glucose and lipid metabolism, increase insulin sensitivity and treat T2DM.To clarify its mechanism and material basis of anti-IR, the spontaneous animal model of IR will be uesed to confirm efficacy of compunds and the best compatibility of medicines;the immune regulation of metabolism of compound prescription and its compatibility is going to explore; the interaction of inflammation cells and immune cells, the correlation of Foxp3 and PPAR-γ will be studied; and inflammation and insulin resistance signaling path way will be analyzed; transgenic animals and cells adoptive transfer model will be used to identify molecular targets of anti-IR and scientificity of Dangguiliuhuang decoction's compatibility.

英文关键词： Dangguiliuhuang decoction;Immunoregulation of metabolism;Insulin resistance;Type 2 diabetes;Compatibility mechanism