Yamaguchi Satoshi, Wiessner John H, Hasegawa Andrew T, Hung Linda Y, Mandel Gretchen S, Mandel Neil S
Department of Medicine, Medical College of Wisconsin and the Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin, USA.
Int J Urol. 2005 Mar;12(3):290-8. doi: 10.1111/j.1442-2042.2005.01038.x.
Although nephrotoxic in high doses, ethylene glycol (EG) has been used with ammonium chloride (NH(4)Cl) or vitamin D(3) to study calcium oxalate stone formation in rat models. In the present study we used EG alone or with NH(4)Cl to study hyperoxaluria, crystaluria, and crystal attachment to renal epithelial cells in rats with minimal renal damage.
Six-week-old male Sprague-Dawley (SD) rats were given food and special drinking water. In experiment 1 the drinking water contained 1.0% NH(4)Cl plus four different concentrations of EG (0.8%, 0.4%, 0.2%, 0.1%). In experiment 2 the drinking water contained EG alone (0.8%, 0.4%, 0.2%, 0.1%). Urine was collected for 24 h before the rats were sacrificed. In experiment 1 the rats were sacrificed 5-13 days after starting the special water. In experiment 2 the rats were sacrificed 7-21 days after starting the special water. Bladder urine was also obtained. Blood and urine were tested for calcium, phosphorus, and creatinine. In addition, urine was tested for pH, oxalate and N-acetyl-beta-D glucosaminidase (NAG). Kidney sections were stained with hematoxylin-eosin, von Kossa and Pizzolato stain. Crystal morphology was determined using polarizing microscopy, and composition was determined using high-resolution X-ray powder diffraction.
Experiment 1: Aggravation of renal function, an increase in urinary oxalate and NAG excretion, and crystals observed in the kidneys all correlated with EG concentration and length of drinking time. In bladder urine, calcium oxalate monohydrate (COM) crystals exceeded calcium oxalate dihydrate (COD) crystals. Experiment 2: Renal function remained unchanged. Oxalate excretion increased and NAG increased slightly. Crystals occurred only in the papillary tip region. Crystals in bladder urine were mostly COD.
In the current rat model, calcium oxalate crystaluria could be induced without severe renal damage in selected cases. Either and/or both COM and COD might form and interact with kidney epithelium. We propose different experimental conditions to study the various phases of calcium oxalate stone formation in young male SD rats.
尽管高剂量的乙二醇(EG)具有肾毒性,但它已被用于与氯化铵(NH₄Cl)或维生素D₃一起,在大鼠模型中研究草酸钙结石的形成。在本研究中,我们单独使用EG或与NH₄Cl一起使用,以研究肾损伤最小的大鼠的高草酸尿症、结晶尿症以及晶体与肾上皮细胞的附着情况。
给六周龄雄性Sprague-Dawley(SD)大鼠提供食物和特殊饮用水。在实验1中,饮用水含有1.0%的NH₄Cl以及四种不同浓度的EG(0.8%、0.4%、0.2%、0.1%)。在实验2中,饮用水仅含有EG(0.8%、0.4%、0.2%、0.1%)。在处死大鼠前收集24小时尿液。在实验1中,在开始饮用特殊水5 - 13天后处死大鼠。在实验2中,在开始饮用特殊水7 - 21天后处死大鼠。还获取膀胱尿液。对血液和尿液进行钙、磷和肌酐检测。此外,检测尿液的pH值、草酸盐和N - 乙酰 - β - D - 氨基葡萄糖苷酶(NAG)。肾脏切片用苏木精 - 伊红、冯·科萨和皮佐拉托染色。使用偏光显微镜确定晶体形态,使用高分辨率X射线粉末衍射确定成分。
实验1:肾功能恶化、尿草酸和NAG排泄增加以及在肾脏中观察到的晶体均与EG浓度和饮用时间长短相关。在膀胱尿液中,一水合草酸钙(COM)晶体超过二水合草酸钙(COD)晶体。实验2:肾功能保持不变。草酸盐排泄增加,NAG略有增加。晶体仅出现在乳头尖区域。膀胱尿液中的晶体大多是COD。
在当前大鼠模型中,在某些选定情况下可诱导出草酸钙结晶尿而无严重肾损伤。COM和COD中的一种和/或两种可能形成并与肾上皮细胞相互作用。我们提出不同的实验条件来研究年轻雄性SD大鼠草酸钙结石形成的各个阶段。