Ito Takamichi, Tanimoto Mitsuo, Yamada Kaori, Kaneko Shigeru, Matsumoto Masakazu, Obayashi Keiko, Hagiwara Shinji, Murakoshi Maki, Aoki Tatsuya, Wakabayashi Michiro, Gohda Tomohito, Funabiki Kazuhiko, Maeda Kunimi, Horikoshi Satoshi, Tomino Yasuhiko
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Nephrology (Carlton). 2006 Feb;11(1):29-35. doi: 10.1111/j.1440-1797.2006.00543.x.
In type 2 diabetic nephropathy, there is no animal model which has been completely matched with humans. Advanced glycation end products (AGE) and transforming growth factor-beta (TGF-beta) are closely related to hyperglycaemia and their pathobiochemistry could explain diabetic nephropathy. The objective of the present study was to evaluate the KK-A(y)/Ta mouse as a suitable model for type 2 diabetic nephropathy including pathological changes and immunohistochemical analyses of AGE and TGF-beta, compared with the non-diabetic BALB/cA mouse.
The urinary albumin/creatinine ratio (ACR), body weight (BW), fasting and casual blood glucose, blood haemoglobin A(1c) (HbA(1c)), creatinine clearance (Ccr) and blood pressure were measured for phenotypic characterisation. The pathological changes of glomeruli were evaluated by light microscopy, immunofluorescence and electron microscopy. AGE and TGF-beta accumulation were evaluated by immunoperoxidase staining.
The mean levels of ACR, casual blood glucose, blood HbA(1c) and Ccr in KK-A(y)/Ta mice were higher than those in age-matched non-diabetic BALB/cA mice after 12 weeks of age. There were no significant changes in the levels of systemic blood pressure among all groups. The pathological changes of glomeruli in KK-A(y)/Ta mice were consistent with those in the early stage of human diabetic nephropathy. AGE and TGF-beta protein appeared to be localised in the glomerular mesangial matrices.
It appears that KK-A(y)/Ta mice, especially in terms of histopathological findings, are a suitable animal model for the early stage of type 2 diabetic nephropathy.
在2型糖尿病肾病中，尚无完全与人类匹配的动物模型。晚期糖基化终产物（AGE）和转化生长因子-β（TGF-β）与高血糖密切相关，其病理生物化学可解释糖尿病肾病。本研究的目的是评估KK-A(y)/Ta小鼠作为2型糖尿病肾病的合适模型，包括与非糖尿病BALB/cA小鼠相比的病理变化以及AGE和TGF-β的免疫组织化学分析。
测量尿白蛋白/肌酐比值（ACR）、体重（BW）、空腹和随机血糖、糖化血红蛋白A1c（HbA1c）、肌酐清除率（Ccr）和血压以进行表型特征分析。通过光学显微镜、免疫荧光和电子显微镜评估肾小球的病理变化。通过免疫过氧化物酶染色评估AGE和TGF-β的积累。
12周龄后，KK-A(y)/Ta小鼠的ACR、随机血糖、血液HbA1c和Ccr的平均水平高于年龄匹配的非糖尿病BALB/cA小鼠。所有组的全身血压水平均无显著变化。KK-A(y)/Ta小鼠肾小球的病理变化与人类糖尿病肾病早期的变化一致。AGE和TGF-β蛋白似乎定位于肾小球系膜基质中。
看来KK-A(y)/Ta小鼠，特别是在组织病理学发现方面，是2型糖尿病肾病早期的合适动物模型。
