胰岛素抵抗慢性移植肾失功大鼠模型的建立及分析  

Establishment and analysis of a rat model of chronic renal allograft dysfunction complicated with insulin resistance

作　　者：吕道远[1,2] 周琴[1,2] 夏悦[1,2] 尤旭[1,2,3] 赵志红[4] 李永强[1,2] 邹和群[1,2] 

机构地区：[1]南方医科大学,广东省广州市510515 [2]南方医科大学第三附属医院肾内科,泌尿疾病研究所,广东省广州市510630 [3]南方医科大学第三附属医院检验科,广东省广州市510630 [4]深圳市人民医院肾内科,广东省深圳市518020

出　　处：《中国组织工程研究》2017年第12期1894-1902,共9页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81270840)~~

摘　　要：背景:慢性移植肾失功的主要病因迄今尚不明确,胰岛素抵抗可能构成其病因之一,然而当前尚缺乏相关动物模型及实验探讨二者的关联。目的:建立胰岛素抵抗慢性移植肾失功大鼠模型,探讨胰岛素抵抗对移植肾肾功能、尿蛋白及病理学改变的影响。方法:在以F344及Lewis大鼠作为供受体的慢性移植肾失功模型基础上予单纯高脂饲料喂养诱发胰岛素抵抗,分别于肾移植术后8,12,16周测定胰岛素抵抗慢性移植肾失功组、慢性移植肾失功组、单肾切除对照组血胰岛素、血糖、血肌酐、尿素氮及24 h尿蛋白,计算胰岛素抵抗指数。同时行口服葡萄糖耐量及胰岛素耐量试验,分别计算血糖-时间曲线下面积,根据3组不同时间点胰岛素抵抗指数、口服葡萄糖耐量及胰岛素耐量试验血糖-时间曲线下面积的差异评估胰岛素抵抗慢性移植肾失功模型建成情况及稳定性。比较胰岛素抵抗慢性移植肾失功组与慢性移植肾失功组血肌酐、尿素氮及24 h尿蛋白的组间差异及不同时间点的差异,于16周行肾脏病理学观察,根据Banff总评分比较3组肾脏病变程度的差异。结果与结论:(1)术后8,12,16周胰岛素抵抗慢性移植肾失功组胰岛素抵抗指数、口服葡萄糖耐量及胰岛素耐量试验血糖-时间曲线下面积均大于慢性移植肾失功组及对照组,且随观察时间延长无显著改变,血肌酐、尿素氮、24 h尿蛋白均小于慢性移植肾失功组,亦随观察时间延长无显著改变;(2)胰岛素抵抗慢性移植肾失功组及慢性移植肾失功组均见肾小球及小管基底膜轻度增厚、间质纤维化及动脉内膜轻度增生等改变,但未见2组肾脏病变程度的显著差异;(3)上述结果提示,使用单纯高脂饲料喂养慢性移植肾失功大鼠8周可构建稳定的胰岛素抵抗慢性移植肾失功模型,胰岛素抵抗可能影响移植肾肾功能及尿蛋白水平,其潜在机制可能涉及胰BACKGROUND：The main cause of chronic renal allograft dysfunction （CRAD） remains unclear until now, and insulin resistance （IR） may be a cause of CRAD. However, there is a lack of an available animal model for research on their association. OBJECTIVE：To establish a rat model of CRAD complicated with IR, and to investigate the effect of IR on function, urinary protein and pathologic changes of the renal allograft. METHODS：The high-fat diet was administrated to a F344-to-Lewis rat model of CRAD to induce IR. There were three groups including CRAD＋IR, CRAD and control （uninephrectomy） groups, and the serum insulin, glucose, creatinine, urea nitrogen and 24-hour urinary protein levels in each group were measured and insulin resistance index was calculated at 8, 12, and 16 weeks after transplantation. Meanwhile, oral glucose tolerance and insulin tolerance tests were performed and the areas under glucose-time curve were calculated. The status and stability of CRAD＋IR models were assessed based on all above indicators at each time point. The serum creatinine, urea nitrogen and 24-hour urinary protein levels were compared between CRAD＋IR and CRAD groups. Pathological evaluation was conducted at 16 weeks based on the total Banff scores. RESULTS AND CONCLUSION：The insulin resistance index, and area under glucose-time curve of the oral glucose tolerance and insulin tolerance tests in the CRAD＋IR group were higher than those in the CRAD and control groups, and all above indexes showed no significant changes with time. The serum creatinine, urea nitrogen and 24-hour urinary protein levels in the CRAD＋IR group were lower than those in the CRAD group, and showed no obvious changes with time. Slightly thickened basement membrane of glomeruli and tubules, interstitial fibrosis and mild arterial intimal hyperplasia were observed both in the CRAD＋IR and CRAD groups, but the pathological degree did not differ notably between the two groups. These results indicate that the stable CRAD＋IR models can b

关 键 词：组织构建 组织工程 慢性移植肾失功 胰岛素抵抗 代谢综合征 动物模型 肾功能 尿蛋白 肾脏病理 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]