基于KKay小鼠模型的罗格列酮治疗2型糖尿病的作用机制研究  

Mechanism study of rosiglitazone in the treatment of type 2 KKay diabetic mice

作　　者：从文娟[1] 沈岚[1,2] 阮克锋[1] 王令仪[1] 朱云云[1] 冯怡[1] 

机构地区：[1]上海中医药大学中药现代制剂技术教育部工程研究中心,上海201203 [2]上海中医药大学中药学院,上海201203

出　　处：《中国新药杂志》2012年第18期2196-2201,2204,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81173516);上海市高校青年教师专项基金(shzy013)

摘　　要：目的:运用代谢组学手段对罗格列酮治疗2型糖尿病的作用机制进行了研究。方法:以KKay糖尿病小鼠为研究对象,对其进行为期8周的罗格列酮灌胃给药治疗,同时以C57BL/6J小鼠作为正常对照。采用UPLC-TOF MS对小鼠的尿液进行代谢组学研究,从机体代谢的角度探究罗格列酮对糖尿病的治疗作用。结果:代谢组学结果表明,KKay小鼠体内的三羧酸循环受抑制,而作为代谢性补偿糖酵解加速。罗格列酮给药后,可以缓解糖酵解的加速现象、对三羧酸循环具有一定的调节作用。结论:采用代谢组学的手段分析尿液中特定代谢物的种类和浓度水平变化,可为罗格列酮治疗2型糖尿病过程中的临床评价提供一种重要的补充方法。Objective：To investigate rosiglitazone’s mechanism in treating type 2 diabetes mellitus（T2DM） in KKay mice via urinary metabonomics.Methods：KKay mice were chosen as the model animals and given with rosiglitazone at a dose of 2 mg·kg-1 by intragastric administration consecutively for 8 weeks,and C57BL/6J mice were used as normal controls.Urine samples were collected after the treatment,and the metabolic profiles of the urine samples were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry（UPLC/TOF-MS）.Then the mechanism underlying rosiglitazone in the treatment of T2DM was investigated from the perspective of global metabolic behaviors.Results：Urinary metabonomic study showed that tricarboxylic acid（TCA） cycle was diminished in the KKay mice,and glycolysis was enhanced as a metabolic compensation.Rosiglitazone treatment inhibited the acceleration of glycolysis and improved TCA cycle.Conclusion：Urine metabonomics analysis revealed the changes of metabolites traits during rosiglitazone treatment,thus providing a supplementary evaluation method for rosiglitazone in the treatment of type II diabetes.

关 键 词：罗格列酮 代谢组学 尿液 KKAY小鼠 2型糖尿病 

分 类 号：R977.15[医药卫生—药品]