青钱柳三萜调控SIRT1/NF-κB信号通路干预肥胖2型糖尿病的效应及机制研究

项目名称： 青钱柳三萜调控SIRT1/NF-κB信号通路干预肥胖2型糖尿病的效应及机制研究

项目编号： No.81503316

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： 蒋翠花

作者单位： 南京中医药大学

项目金额： 18万元

中文摘要： 肥胖2型糖尿病面临血糖波动、体重增加、胰岛β细胞功能紊乱等多重难题，目前临床上缺乏有效的治疗方法及药物。中医认为“阴津亏损、中满内热”为肥胖2型糖尿病主要病机，现代医学证实肥胖诱导的慢性炎症是其发病的关键因素。中草药青钱柳具有清热解毒，生津止渴的功效，对消渴症具有良好的治疗效果。本课题组前期研究证明青钱柳具有抑制炎性胰岛素抵抗，治疗肥胖2型糖尿病的效果。青钱柳三萜是其有效成分，并通过激活SIRT1发挥治疗作用。SIRT1在肥胖诱导的慢性炎症中作用已被证实，但是青钱柳三萜如何通过SIRT1调控炎症干预肥胖2型糖尿病的作用机理尚待研究。本项目拟以SIRT1活性作为切入点，在整体动物、细胞水平上建立炎性胰岛素抵抗模型体系，通过基因沉默、蛋白免疫印迹等技术，揭示青钱柳三萜通过调控SIRT1/NF-κB通路对肥胖2型糖尿病的干预效应及作用机理。本课题的实施为中医药治疗肥胖2型糖尿病提供新思路和新方法

中文关键词： 肥胖2型糖尿病；慢性炎症；胰岛素抵抗；沉默信息调节因子1；青钱柳

英文摘要： Obese type 2 diabetic patients are challenged with weight gain, glucose variability and disorder of β-cell function in the pancreas, for which effective therapies and medicines are still lacking. Based on the traditional Chinese medicine theory, ‘damp’ and ‘heat’ are main pathological factors associated with obese type 2 diabetes. Modern medicine confirms that obesity-induced chronic inflammation is a key factor in the pathogenesis of obese type 2 diabetes. Cyclocarya paliurus is a traditional herb with Qingrejiedu (to clear heat and toxin) and Shengjinzhike (to help produce saliva and slake thirst) efficiency and it is reported to be of significant effects for the treatment of diabetes. Our previous findings revealed that Cyclocarya paliurus can inhibit inflammation-related insulin resistance and treat of obese type 2 diabetes. Triterpenoids might be its active components, which exert therapeutic effects through activation SIRT1. The important roles of SIRT1 in treatment of obesity-induced chronic inflammation has been confirmed. However, the mechanism that triterpenoids modulate this disease through SIRT1/NF-κB pathways remains unknown. In the present study, we will prepare a model system of adipose inflammation-related insulin resistance and establish the link between NF-κB and adipokines by focusing on the regulation of SIRT1 with possible methods such as siRNA technique, western blot analysis. Using these models as platforms, we will investigate the effect and mechanism of the triterpenoids from Cyclocarya paliurus on ameliorating obese type 2 diabetes. This study is conductive to provide new ideas and new ways for Chinese medicine in treatment of obesity type 2 diabetes.

英文关键词： obese type 2 diabetes;chronic inflammation;insulin resistance;sirtuin type 1 ;Cyclocarya paliurus