中药糖耐康调节A1AT-NE平衡信号改善中性粒细胞介导的脂肪胰岛素抵抗作用机制研究

项目名称： 中药糖耐康调节A1AT-NE平衡信号改善中性粒细胞介导的脂肪胰岛素抵抗作用机制研究

项目编号： No.81503455

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 孙文

作者单位： 北京中医药大学

项目金额： 18万元

中文摘要： 胰岛素抵抗是肥胖、2型糖尿病等多种代谢性疾病的共同发病基础。A1AT-NE信号失衡是中性粒细胞介导脂肪细胞胰岛素抵抗的重要途径。糖耐康是临床有效的治疗T2DM胰岛素抵抗的中药复方，其分子机制的研究不够深入。课题组前期的研究发现糖耐康含药血清能够调节3T3-L1脂肪细胞炎症状态改善胰岛素抵抗，基因组学数据挖掘也发现糖耐康能够下调GK大鼠脂肪组织的炎症反应、中性粒细胞趋化性、T细胞增殖等功能基因，我们推测糖耐康能够调节A1AT-NE信号失衡。因此，本项目在前期基础上，进一步以ob/ob小鼠和3T3-L1脂肪细胞胰岛素抵抗模型为研究对象，分析糖耐康能否升高A1AT水平，降低NE水平，调节下游PI3K、AMPK信号的关键位点，以发现糖耐康改善中性粒细胞介导的脂肪组织胰岛素抵抗的作用机制，为中药抗胰岛素抵抗研究奠定实验基础。

中文关键词： 糖耐康；A1AT-NE平衡；中性粒细胞；脂肪；胰岛素抵抗

英文摘要： Insulin resistance is a common pathogenetic basis of various metabolic diseases including obesity and type II diabetes. The pathogenetic mechanism of insulin resistance in type II diabetes and the research and development of drugs improving insulin resistance have become the leading edge and hotspot of pharmaceutical researches. Inflammation of adipose tissue is an important factor in insulin resistance, and neutrophils-mediated adipocyte insulin resistance is the new hotspot of research. The latest research shows that improving neutrophils-mediated adipocyte insulin resistance through regulating A1AT-NE balance signal plays an important role in the pathogenesis of insulin resistance in type II diabetes. The Tangnaikang presents a definite anti-diabetic effect. However, researches on the hypoglycemic mechanism and targets of Tangnaikang are lack of depth and its mechanism remains to be elucidated. It was discovered in our preliminary study that Tangnaikang had an effect on improving insulin resistance in the 3T3-L1 cell. This project will take full advantage of molecular biological techniques further to study the molecular mechanisms of Tangnaikang in improving neutrophils-mediated adipocyte insulin resistance through regulating A1AT-NE balance signal and lay an important foundation for the research and development of new drugs.

英文关键词： Tangnaikang;Balance between neutrophil elastase and alpha1-antitrypsin;Neutrophils;Adipose;Insulin resistance