胰岛素抵抗慢性移植肾失功大鼠模型的建立及分析

发布时间：2018-02-27 07:34

  本文关键词： 肾移植 肾机能不全 移植物存活 胰岛素 代谢综合征X 疾病模型 动物 组织工程 组织构建 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　出处：《中国组织工程研究》2017年12期 　论文类型：期刊论文

【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岛素抵抗环境下肾小球的高滤过及肾小管对尿蛋白的超负荷重吸收。
[Abstract]:Background: the main causes of chronic renal allograft dysfunction are still unclear, and insulin resistance may be one of its causes. However, there is still a lack of related animal models and experimental study on the relationship between them. Objective: to establish a model of chronic renal allograft dysfunction in rats with insulin resistance, and to explore the effect of insulin resistance on renal function. Methods: on the basis of chronic renal allograft failure model with F344 and Lewis rats as donor recipients, insulin resistance was induced by high fat diet alone. Serum insulin, blood glucose, serum creatinine, urea nitrogen and 24 h urine protein were measured in chronic allograft failure group, chronic allograft failure group and single nephrectomy control group at 812 weeks after renal transplantation. The insulin resistance index was calculated. Oral glucose tolerance test and insulin tolerance test were used to calculate the area under the glycemic time curve, and the insulin resistance index was calculated according to the different time points in the three groups. The difference of the area under the blood glucose curve between oral glucose tolerance test and insulin tolerance test the establishment and stability of chronic renal allograft failure model of insulin resistance were compared between chronic insulin resistance renal allograft failure group and chronic renal allograft failure group. Serum creatinine in patients with renal allograft dysfunction, The difference of urea nitrogen and 24 h urine protein and the difference of different time points were observed at 16 weeks. Results and conclusion the insulin resistance index of chronic renal allograft failure group was 812 ~ 16 weeks after operation. The area under the glycemic time curve of oral glucose tolerance test and insulin tolerance test was larger than that of chronic renal allograft failure group and control group. Urinary protein in 24 h of urea nitrogen group was lower than that in chronic allograft group, and there was no significant change with the prolongation of observation time) glomerular and tubule basement membrane thickened slightly in both chronic allograft and chronic allograft failure group, and insulin resistance group showed slight thickening of glomerular and microtubule basement membrane. Interstitial fibrosis and mild intimal hyperplasia, but no significant difference in the degree of renal lesions between the two groups. A stable model of chronic renal allograft failure with insulin resistance could be established by feeding chronic allograft dysfunction rats with high fat diet for 8 weeks. Insulin resistance may affect renal function and urinary protein level. The underlying mechanism may involve high filtration of glomeruli and overloaded reabsorption of urinary proteins by renal tubules in insulin-resistant environment.
【作者单位】： 南方医科大学;南方医科大学第三附属医院肾内科泌尿疾病研究所;南方医科大学第三附属医院检验科;深圳市人民医院肾内科;
【基金】：国家自然科学基金(81270840)~~
【分类号】：R-332;R699.2
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