Scherzer Pnina, Katalan Shachaf, Got Gay, Pizov Galina, Londono Irene, Gal-Moscovici Anca, Popovtzer Mordecai M, Ziv Ehud, Bendayan Moise
Nephrology and Hypertension Unit, Hadassah University Hospital, Jerusalem, Israel.
Anat Cell Biol. 2011 Sep;44(3):176-85. doi: 10.5115/acb.2011.44.3.176. Epub 2011 Sep 29.
The Psammomys obesus lives in natural desert habitat on low energy (LE) diet, however when maintained in laboratory conditions with high energy (HE) diet it exhibits pathological metabolic changes resembling those of type 2 diabetes. We have evaluated and correlated the histopathology, metabolic and functional renal alterations occurring in the diabetic Psammomys. Renal function determined by measuring glomerular filtration rate (GFR), protein excretion, protein/creatinine ratio and morpho-immunocytochemical evaluations were performed on HE diet diabetic animals and compared to LE diet control animals. The diabetic animals present a 54% increase in GFR after one month of hyperglycemic condition and a decrease of 47% from baseline values after 4 months. Protein excretion in diabetic animals was 5 folds increased after 4 months. Light microscopy showed an increase in glomeruli size in the diabetic Psammomys, and electron microscopy and immunocytochemical quantitative evaluations revealed accumulation of basement membrane material as well as frequent splitting of the glomerular basement membrane. In addition, glycogen-filled Armanni-Ebstein clear cells were found in the distal tubules including the thick ascending limbs of the diabetic animals. These renal complications in the Psammomys, including changes in GFR with massive proteinuria sustained by physiological and histopathological changes, are very similar to the diabetic nephropathy in human. The Psamommys obesus represents therefore a reliable animal model of diabetic nephropathy.
肥胖沙鼠生活在天然沙漠栖息地,以低能量(LE)饮食为生,然而,当在实验室条件下以高能量(HE)饮食饲养时,它会出现类似于2型糖尿病的病理性代谢变化。我们已经评估了糖尿病肥胖沙鼠发生的组织病理学、代谢和功能性肾脏改变,并将它们相互关联起来。对食用HE饮食的糖尿病动物进行了通过测量肾小球滤过率(GFR)、蛋白质排泄、蛋白质/肌酐比值来确定的肾功能以及形态免疫细胞化学评估,并与食用LE饮食的对照动物进行比较。糖尿病动物在高血糖状态1个月后GFR增加54%,4个月后比基线值降低47%。糖尿病动物4个月后蛋白质排泄增加了5倍。光学显微镜显示糖尿病肥胖沙鼠的肾小球大小增加,电子显微镜和免疫细胞化学定量评估显示基底膜物质积聚以及肾小球基底膜频繁分裂。此外,在糖尿病动物的远端小管包括髓袢升支粗段中发现了充满糖原的阿-埃氏透明细胞。肥胖沙鼠的这些肾脏并发症,包括GFR变化以及由生理和组织病理学变化导致的大量蛋白尿,与人类糖尿病肾病非常相似。因此,肥胖沙鼠是糖尿病肾病的可靠动物模型。