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在链脲佐菌素诱导的糖尿病肾病大鼠模型中,胰岛移植可修复肾小球滤过膜损伤。

Islet transplantation restores the damage of glomerulus filtration membrane in a rat model of streptozotocin-induced diabetic nephropathy.

作者信息

Ziqiang Xu, Yunqiang He, Hongxing Fu, Jinjun Wang, Yong Cai

机构信息

Transplantation Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

J Pak Med Assoc. 2016 Mar;66(3):296-301.

Abstract

OBJECTIVE

To evaluate the effects on filtration membrane of glomerulus after islet transplantation in a rat model of streptozotocin-induced diabetic nephropathy.

METHODS

The experimental case-control study was conducted at Wenzhou Medical University, Wenzhou, China from January to May 2015, and comprised male Sprague Dawley rats obtained from the Laboratory Animal Centre of Wenzhou Medical University. The rats were intraperitoneally injected with streptozotocin to induce diabetic nephropathy. Diabetic rats were divided into two groups; the islets group received islets transplantation under the kidney capsule; and the diabetic nephropathy (DN) group consisted of untreated diabetic nephropathy rats. The control group consisted of non-diabetic rats. Islets were surgically transplanted under the kidney capsule. Kidney function and blood glucose were measured and pathological changes in the kidney were observed by electron microscope, while the expressions of Wilms' tumour-1, caspase-3 and transforming growth factor-beta 1 were tested by immunohistochemical method and Western blot analysis.

RESULTS

Each of the three groups had 6 rats each with body weights ranging from 180g to 220g. Reduced urinary protein excretion and alleviated damage of podocytes and glomerular basement membrane were seen in the islet-transplanted rats. The alleviation of podocyte damage was related to alteration in the synthesis of caspase-3, transforming growth factor-beta 1, and Wilms' tumour-1 protein in the glomerulus.

CONCLUSIONS

Diabetic nephropathy rats after islet transplantation can ameliorate the damage of podocytes and basement membrane by inhibiting the pathway of transforming growth factor-beta 1.

摘要

目的

在链脲佐菌素诱导的糖尿病肾病大鼠模型中,评估胰岛移植对肾小球滤过膜的影响。

方法

2015年1月至5月在温州医科大学进行了实验性病例对照研究,所用雄性斯普拉格-道利大鼠购自温州医科大学实验动物中心。大鼠腹腔注射链脲佐菌素诱导糖尿病肾病。糖尿病大鼠分为两组;胰岛移植组在肾被膜下进行胰岛移植;糖尿病肾病(DN)组为未治疗的糖尿病肾病大鼠。对照组为非糖尿病大鼠。通过手术将胰岛移植到肾被膜下。检测肾功能和血糖,用电子显微镜观察肾脏病理变化,同时采用免疫组织化学方法和蛋白质印迹分析检测肾母细胞瘤蛋白-1、半胱天冬酶-3和转化生长因子-β1的表达。

结果

三组每组各有6只大鼠,体重范围为180克至220克。胰岛移植大鼠的尿蛋白排泄减少,足细胞和肾小球基底膜损伤减轻。足细胞损伤的减轻与肾小球中半胱天冬酶-3、转化生长因子-β1和肾母细胞瘤蛋白-1合成的改变有关。

结论

胰岛移植后的糖尿病肾病大鼠可通过抑制转化生长因子-β1途径改善足细胞和基底膜的损伤。

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