Chen A, Sheu L F, Ho Y S, Lin Y F, Chou W Y, Chou T C, Lee W H
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Nephron. 1998;78(4):440-52. doi: 10.1159/000044974.
Although a lot of animal models of proteinuria have been established, proposals for the mechanisms of proteinuria are still controversial. In this work, during an 18-day trial, mice injected with a single dose of adriamycin (AD) rapidly showed combined glomerular albuminuria and immunoglobulinuria, progressively elevated levels of nitrite/nitrate in urine, hypercholesterolemia, abnormal renal function, segmentally or globally glomerular hyalinosis/sclerosis associated with tubular atrophy, enhanced glomerular deposition of immunoglobulins and fibrinogen, augmented expression of matrix components in the whole glomerular tuft, and loss of glomerular negative charge property. These laboratory and pathological features are comparatively similar to those of human focal segmental glomerulosclerosis in the advanced state. Juxtamedullary glomeruli appear to be more susceptible to the AD-related nephrotoxicity than those in the superficial renal cortex. A change in size-dependent glomerular permselectivity may precede a charge-dependent defect in glomeruli in this mouse model of proteinuria. Data in this study confirm the hypothesis of glomerular hyperfiltration involved in the pathogenesis of this chronic glomerulopathy associated with proteinuria in mice. In addition, nitric oxide may play a crucial role in the progression of the chronic glomerulopathy model.
尽管已经建立了许多蛋白尿的动物模型，但关于蛋白尿机制的提议仍存在争议。在这项研究中，在为期18天的试验期间，单次注射阿霉素（AD）的小鼠迅速出现了肾小球性白蛋白尿和免疫球蛋白尿，尿中亚硝酸盐/硝酸盐水平逐渐升高，高胆固醇血症，肾功能异常，与肾小管萎缩相关的节段性或全球性肾小球玻璃样变/硬化，免疫球蛋白和纤维蛋白原在肾小球的沉积增加，整个肾小球毛细血管襻中基质成分的表达增加，以及肾小球负电荷特性丧失。这些实验室和病理特征与晚期人类局灶节段性肾小球硬化的特征较为相似。与浅表肾皮质的肾小球相比，近髓肾小球似乎更容易受到与AD相关的肾毒性影响。在这个蛋白尿小鼠模型中，大小依赖性肾小球滤过选择性的变化可能先于肾小球电荷依赖性缺陷。本研究的数据证实了肾小球高滤过参与小鼠这种与蛋白尿相关的慢性肾小球病发病机制的假说。此外，一氧化氮可能在慢性肾小球病模型的进展中起关键作用。
