Kumar S, Sigmon D, Miller T, Carpenter B, Khan S, Malhotra R, Scheid C, Menon M
Division of Urology and Transplantation Surgery, University of Massachusetts Medical School, Worcester.
J Urol. 1991 Nov;146(5):1384-9. doi: 10.1016/s0022-5347(17)38120-x.
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 conducive to the formation and growth of calcium oxalate stones.
为了更好地理解肾结石的发病机制，我们建立了一种新的动物模型，该模型能紧密模拟人类草酸钙结石病。给大鼠采用一种联合治疗方案，即适度高草酸尿症（通过喂食3%草酸铵10天产生）与轻度近端肾小管损伤/功能障碍（通过每日注射硫酸庆大霉素-40毫克/千克，共8天产生）相结合。与单独用草酸盐或庆大霉素治疗的动物相比，这种联合治疗使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来评估肾脏冠状切片中晶体的丰度，我们发现接受庆大霉素加草酸盐治疗的动物中有63%显示“中等”数量的晶体，而单独接受草酸盐治疗的动物中这一比例为8%；并且大多数晶体出现在乳头，这一模式与人类结石病中所见相似。未治疗的大鼠和单独用庆大霉素治疗的大鼠未出现草酸钙晶体或结石。尽管有大量的晶体和结石，但通过肌酐清除率判断，接受庆大霉素加草酸盐治疗的动物肾功能仍相对正常。因此，该模型相对于现有的肾结石模型有几个优点。晶体和结石沉积迅速发展（在14天内）。沉积模式与人类结石病中所见相似，并且肾功能保持相对正常。这些发现表明，这种肾结石模型可能对结石病发病机制的研究有用。此外，它们表明肾小管损伤和/或功能障碍可能产生有利于草酸钙结石形成和生长的条件。
