骨骼肌特异性胰岛素样生长因子1及胰岛素双受体功能缺失鼠糖尿病发病及其相关炎症因子的变化  

Development of diabetes and inflammatory factors in mice with skeletal muscle-specific inactivation of insulin-like growth factor 1 and insulin receptors

作　　者：喻嵘[1] 成细华[1] 胡伟[1] 肖曼江[1] Jun-Li LiuO 

机构地区：[1]湖南中医药大学基础医学院,湖南省长沙市410007 [2]Laboratones,Department of Medicine, McGill University,Montreal, QC,Canada （687 PineAvenue West,MontreaI,QC H3A1A1 ）

出　　处：《中国组织工程研究与临床康复》2007年第45期9075-9078,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家自然科学基金(30400604);国家中医药管理局回国留学人员项目(国中医药发[2004]68号-1);湖南省教育厅重点项目(04A040)~~

摘　　要：目的:临床研究表明,2型糖尿病及其并发症患者,均可出现炎症反应标志物的异常改变。观察骨骼肌胰岛素样生长因子1受体及胰岛素受体功能缺失转基因2型糖尿病小鼠的糖代谢及其相关炎症因子的变化。方法:实验于2005-11/2006-08在湖南中医药大学SPF实验动物中心及血管生物学实验室(国家三级实验室)完成。①实验材料:由美国国立卫生研究院(NIH)授权使用引进的10只MKR鼠,经自然交配后繁殖的子代28只及30只C57小鼠。②实验方法:对MKR鼠进行鉴定后,从MKR鼠子代出生第3周开始每周定时以电化学法血糖仪进行血糖检测。③实验评估:观察2月龄MKR鼠血糖及胰岛素的水平;双抗体夹心ELISA法检测3月龄MKR鼠细胞间黏附分子1、血管内皮黏附分子1、脂联素的变化。同期采用C57小鼠进行对照。结果:纳入由10只MKR鼠经自然交配后繁殖的子代28只,经鉴定后22只纳入实验观察;C57小鼠30只,相关炎症分子检测的实验中有2例因血液样本溶血剔除,其余均进入结果分析。①MKR鼠所有子代鼠均会出现长度为330bp的DNA片断,表明该MKR鼠后代能稳定遗传。②新生MKR鼠自出生3周开始,即出现显著的血糖增高,5周以后血糖则较稳定地维持在高水平。MKR鼠在2月龄时即表现出显著的高胰岛素血症及糖耐量低下,与C57对照组小鼠比较,差异具有非常显著性意义(P<0.01)。③MKR鼠的脂联素含量显著升高,而细胞间黏附分子1、血管内皮黏附分子1含量亦显著增高,与C57对照组小鼠相比,差异具有非常显著性意义(P<0.01)。结论:本文成功地引进了MKR模型,MKR鼠是目前一种非常良好的2型糖尿病动物模型,并具有明显的炎症反应特征。AIM： The patients with type 2 diabetes and complications appear the abnormal markers of inflammatory reaction in clinics. This study is designed to examine the changes of the circulating glucose and inflammatory factors in the mice, in which the deficiencies of insulin-like growth factor （IGF）-1 receptor and insulin receptor in the skeletal muscle lead to systemic insulin resistance and diabetes. METHODS： From Novermber 2005 to August 2006, the experiment was carried out in the SPF-grade Animal Experimental Center and Vascular Biology Laboratory （National Level-Three Laboratory） in the Hunan University of Traditional Chinese Medicine.①Ten MKR mice were imported from the National Institutes of Health （USA）, 28 offspring MKR mice and 30 C57 mice.②The identified MKR mice were followed on blood glucose level once a week from the third weeks.③Using C57 mice as controls, the blood glucose level and insulin level were detected in 2-month MKR mice; the intracellular adhesion molecule factor 1, vascular endothelial adhesion molecule and adiponectin were determined in in 3-month MKR mice. RESULTS： Totally 28 offspring MKR mice and 30 C57 mice were involved in the study, and 22 identified MKR mice and 28 C57 mice entered the analysis. ①All the offspring of MKR mice exhibited DNA segment of 330 bp, indicating the stable transgenic hereditary.②These offspring mice were hyperglycaemic from the third week of age and remained in the high level 5 weeks later; there were extremely significant differences in the hyperinsulinemia and glucose intolerance in 2-month MKR mice and C57 mice （P 〈 0.01）.③Compared with C57 mice, the MKR mice also presented an extremely significant increase of the intracellular adhesion molecule factor 1, vascular endothelial adhesion molecule and adiponectin （P 〈 0.01）. CONCLUSION; The MKR model has been estabolished successfully, and it is of characteristics on the Type-2 diabetes and inflammation reaction.

关 键 词：2型糖尿病 转基因技术 胰岛素样生长因子1受体 胰岛素受体 炎症因子 

分 类 号：R587.1[医药卫生—内分泌]