A NEW MODEL OF NEPHROLITHIASIS INVOLVING TUBULAR DYSFUNCTION INJURY
A NEW MODEL OF NEPHROLITHIASIS INVOLVING TUBULAR DYSFUNCTION INJURY
复制标题
DOI：
10.1016/s0022-5347(17)38120-x
复制
发表时间：
1991-11-01
影响因子：
6.6
通讯作者：
MENON, M
中科院分区：
文献类型：
--
作者：
KUMAR, S;SIGMON, D;MENON, M
为了更好地了解肾结石的发病机制，我们开发了一种新的动物模型，密切模仿人类草酸钙结石病。大鼠用一种方案治疗，该方案将中度高尿症（通过用3%草酸铵喂养10天产生）与轻度近端肾小管损伤/功能障碍（通过每天8次注射硫酸庆大霉素-40 mg/kg产生）相结合。kg.）。与草酸盐或庆大霉素单独给药的动物相比，这种联合给药导致草酸钙晶体和结石的发生率显著增加。使用半定量评分系统估计晶体的丰度在冠状面的肾脏，我们发现，63%的动物接受庆大霉素加草酸盐显示“中等”数量的晶体，相比之下，8%的动物接受草酸盐单独和大多数的晶体发生在乳头，一种模式类似于在人类结石病。未处理的大鼠和单独用庆大霉素处理的大鼠未显示草酸钙晶体或结石。尽管晶体和结石丰富，接受庆大霉素加草酸盐的动物保留相对正常的肾功能，通过肌酐清除率判断。因此，该模型与先前存在的肾结石模型相比具有几个优点。晶体和结石沉积发展迅速（14天内）。沉积模式类似于人类结石病，肾功能保持相对正常。这些结果表明，这种肾结石模型可能被证明是有用的结石病的发病机制的研究。此外，他们认为，肾小管损伤和/或功能障碍可能产生的条件下，草酸钙结石的形成和生长的传导。
To better understand the pathogenesis of nephrolithiasis, we developed a new animal model that closely mimics human calcium oxalate stone disease. Rats were treated with a regimen that combines moderate hyperoxaluria (produced by 10 days of feeding with 3% ammonium oxalate) with mild proximal tubular injury/dysfunction (produced by 8 daily injections of gentamicin sulfate -40 mg./kg.). This combined treatment caused a marked increase in the incidence of calcium oxalate crystals and stones over that seen in animals treated with oxalate or gentamicin alone. Using a semiquantitative scoring system for estimating the abundance of crystals in coronal sections of kidneys, we found that 63% of animals receiving gentamicin plus oxalate showed "moderate" numbers of crystal, as compared to 8% of animals receiving oxalate alone; and the majority of the crystals occurred in the papilla, a pattern similar to that seen in human stone disease. Untreated rats and rats treated with gentamicin alone did not exhibit calcium oxalate crystals or stones. Despite the abundance of crystals and stones, animals receiving gentamicin plus oxalate retained relatively normal renal function as judged by creatinine clearance. Thus, the model has several advantages over preexisting models of nephrolithiasis. Crystal and stone deposition develop rapidly (within 14 days). The pattern of deposition resembles that seen in human stone disease and renal function remains relatively normal. These findings indicate that this model of nephrolithiasis may prove useful for studies of the pathogenesis of stone disease. Moreover, they suggest that renal tubular injury and/or dysfunction may produce conditions conductive to the formation and growth of calcium oxalate stones.