中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (12): 1894-1902.doi: 10.3969/j.issn.2095-4344.2017.12.016

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

胰岛素抵抗慢性移植肾失功大鼠模型的建立及分析

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   

  1. 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
  • 收稿日期:2017-02-13 出版日期:2017-04-28 发布日期:2017-05-16
  • 通讯作者: 邹和群，教授，博士生导师，主任医师，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
  • 作者简介:吕道远，男，1990年生，江苏省连云港市人，汉族，南方医科大学在读硕士，主要从事慢性移植肾失功研究。
  • 基金资助:

    国家自然科学基金(81270840)

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

Lv Dao-yuan1, 2, Zhou Qin1, 2, Xia Yue1, 2, You Xu1, 2, 3, Zhao Zhi-hong4, Li Yong-qiang1, 2, Zou He-qun1, 2   

  1. 1Southern Medical University, Guangzhou 510515, Guangdong Province, China; 2Department of Nephrology, Institution of Urology and Nephrology, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China; 3Department of Clinical Laboratory, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China; 4Department of Nephrology, Shenzhen People’s Hospital, Shenzhen 518020, Guangdong Province, China
  • Received:2017-02-13 Online:2017-04-28 Published:2017-05-16
  • Contact: Zou He-qun, Professor, Doctoral supervisor, Chief physician, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Department of Nephrology, Institution of Urology and Nephrology, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China
  • About author:Lv Dao-yuan, Studying for master’s degree, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Department of Nephrology, Institution of Urology and Nephrology, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81270840

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摘要：

文章快速阅读：

文题释义：
慢性移植肾失功：指接受移植后至少3-6个月，特别是1年或数年后，移植肾出现的进行性功能减退及形态学病变，最终移植肾功能衰竭，受者恢复肾脏替代治疗，它是影响移植肾长期存活的首要原因，其病因目前尚不完全明确。
胰岛素抵抗：指机体组织细胞对胰岛素的敏感性下降及胰岛素促进靶器官葡萄糖摄取和利用作用减低的一种状态，其构成代谢综合征的中心环节及基本特征，有观点认为代谢综合征/胰岛素抵抗可能构成慢性移植肾失功的病因之一。
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。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程
ORCID: 0000-0001-8662-6060(吕道远)

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

Abstract:

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 be established via feeding CRAD rats with high-fat diet for 8 weeks. IR can cause glomerular hyperfiltration and albumin overload-induced tubular injury which may potentially affect the function and urinary protein level of the renal allograft.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words:  Kidney Transplantation, Renal Insufficiency, Graft Survival, Insulin Resistance, Metabolic Syndrome X, Disease Models, Animal, Tissue Engineering

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