基于TLRs/NF-κB信号通路的“黄芩-黄连”药对防治胰岛素抵抗作用机制研究

项目名称： 基于TLRs/NF-κB信号通路的“黄芩-黄连”药对防治胰岛素抵抗作用机制研究

项目编号： No.81460622

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 涂秀英

作者单位： 江西中医药大学

项目金额： 47万元

中文摘要： 2型糖尿病胰岛素抵抗（IR），多由长期过食肥甘，肠道菌群失调，炎性反应，终致内热，与信号通路TLRs/NF-κB障碍有关。我们发现，清热燥湿经典药对黄芩-黄连能降低血糖，方中成份小檗碱可增加葡萄糖消耗量，又据文献报道，黄芩苷和小檗碱可抑制NF-κB 活化，且小檗碱可改善肠道菌群结构，减轻慢性炎症，治疗糖尿病。本课题提出黄芩-黄连药对（SC)治疗IR作用，可能与TLRs/NF-κB信号通路有关（假说）；拟通过KKAy糖尿病小鼠，3T3-L1脂肪细胞胰岛素抵抗和RAW264.7巨噬细胞炎症模型，以及这两种细胞共培养实验，观测SC干预TLRs/NF-κB信号通路防治胰岛素抵抗作用。结合Western blot法检测蛋白水平，荧光定量PCR法测mRNA表达量，变性梯度凝胶电泳法分析肠道菌群，在原工作基础上，进一步分析SC治疗胰岛素抵抗可能信号机制，为中医药治疗IR提供新靶点和新途径。

中文关键词： “黄芩-黄连”药对；胰岛素抵抗；信号转导；TLRs；/；NF-κB；作用机制

英文摘要： The principal pathogenesis of insulin resistance (IR) of type 2 diabetes mellitus of chinese medical science is dryness-heat abundance because of high fat diet, alteration of intestinal flora,inflammatory reaction. Which is related with the disturbance of intracellular TLRs/NF-κB signal pathway of glucose transport. We discovered that scutellaria-coptis herb couple significantly decreased blood sugar and berberine can increase glucose consumption;according to reports in the literature, baicalin and berberine can inhibit NF-κB activation, and berberine can improve the intestinal flora, reduce chronic inflammation, and treat diabetes. we propose hypothesis that the effect of anti-insulin resistance of type 2 diabetes mellitus is related with the TLRs/NF-κB signal pathway.We will observe the mechanism of TLRs/NF-κB signal transduction of insulin resistance of type 2 diabetes mellitus by diabetic KKAy mice model, two representative cell model (3T3-L1 cells and RAW264.7 macrophages）,the co-culture of these two kinds of cells,and by using ELISA,western blot,fluorescence quantitative PCR, denaturant gradient gel electrophoresis technology and so on. Further analysis of the mechanism of signal transduction of scutellaria-coptis herb couple in the treatment of insulin resistance,which would provide new approach and new target for prevention and cure of IR.

英文关键词： Scutellaria-coptis herb couple;insulin resistance;signal transduction;TLRs/NF-κB;mechanism of action