Faulhaber-Walter Robert, Jiang Lanping, Mizel Diane, Zerfas Patricia M, Kopp Jeffrey B, Schnermann Jurgen B, Chen Limeng, Schiffer Mario
Facharztzentrum Aarberg, Waldshut-Tiengen, Germany.
NIDDK, National Institutes of Health, Bethesda, MD, USA.
Int J Nephrol Renovasc Dis. 2020 Feb 21;13:19-26. doi: 10.2147/IJNRD.S203810. eCollection 2020.
To investigate podocyte density in aging diabetic Ins2± and Ins2±, A1AR-/- mouse models in C57Bl/6 background.
Ins2± mice and especially Ins2±, adenosine A1 receptor knockout mice (Ins2±, A1AR-/-) are mouse models with a phenotype of diabetic nephropathy. Aged mice (at ~40 weeks) were assessed for glomerular filtration barrier function by measuring albuminuria, glomerular filtration, glomerular damage by electron microscopy, and podocyte numbers by Wilms Tumor protein (WT-1) staining.
Compared to healthy wild-type mice, both diabetic mouse models developed diabetic nephropathy, including hyperfiltration (p<0.01) and albuminuria (p<0.05). Typical diabetic structural glomerular and podocyte damage was visualized by electron microscopy. Podocyte count per glomerular area (podocyte density) was significantly decreased in both diabetic mouse models (p<0.01). In contrast, no significant correlation was detected between albuminuria and absolute podocyte count per glomerulus.
The amount of albuminuria as marker of diabetic nephropathy does not correlate with the podocytes density; however, a relative podocyte deficiency became evident with an increase in glomerular area in the diabetic animals, suggesting a relative podocytopenia.
在C57Bl/6背景下的衰老糖尿病Ins2±和Ins2±、A1AR-/-小鼠模型中研究足细胞密度。
Ins2±小鼠，尤其是腺苷A1受体敲除小鼠（Ins2±，A1AR-/-）是具有糖尿病肾病表型的小鼠模型。对老年小鼠（约40周龄）通过测量蛋白尿、肾小球滤过、电子显微镜下的肾小球损伤以及用肾母细胞瘤蛋白（WT-1）染色评估足细胞数量，来评估肾小球滤过屏障功能。
与健康野生型小鼠相比，两种糖尿病小鼠模型均出现了糖尿病肾病，包括超滤（p<0.01）和蛋白尿（p<0.05）。通过电子显微镜观察到典型的糖尿病性肾小球和足细胞结构损伤。两种糖尿病小鼠模型中每个肾小球区域的足细胞计数（足细胞密度）均显著降低（p<0.01）。相比之下，未检测到蛋白尿与每个肾小球足细胞绝对计数之间存在显著相关性。
作为糖尿病肾病标志物的蛋白尿水平与足细胞密度无关；然而，随着糖尿病动物肾小球面积的增加，相对足细胞缺乏变得明显，提示存在相对足细胞减少。
