Abramowsky C R, Aikawa M, Swinehart G L, Snajdar R M
Am J Pathol. 1984 Dec;117(3):400-8.
Advances in our understanding of the mechanisms of proteinuria in humans have depended on a variety of animal models. Most of these have been partially satisfactory because they require pretreatment of the animal with chemicals or toxins or they depend on an aging-related glomerular protein leakiness. The strain in this study was obtained by Koletsky after selective inbreeding of the offspring from a hypertensive Kyoto-Wistar and a normotensive Sprague-Dawley rat. The affected animals appear in 25% of the litters, indicating an autosomal recessive gene, and present with a spontaneous and progressive nephrotic syndrome detected as early as 3-5 weeks and associated with obesity, hypertension, hypoalbuminemia, hypercholesterolemia, and hyperlipidemia. Preliminary morphologic and immunofluorescence studies of their kidneys show progressive glomerular segmental sclerotic lesions and prominent mesangial deposition of IgM, a picture which resembles a steroid-resistant form of idiopathic nephrotic syndrome in humans, namely, focal glomerular sclerosis.
我们对人类蛋白尿机制认识的进展依赖于多种动物模型。其中大多数只是部分令人满意，因为它们需要用化学物质或毒素对动物进行预处理，或者依赖于与衰老相关的肾小球蛋白渗漏。本研究中的品系是科莱茨基通过对一只高血压京都-威斯塔大鼠和一只正常血压的斯普拉格-道利大鼠的后代进行选择性近亲繁殖获得的。受影响的动物出现在25%的窝中，表明是常染色体隐性基因，早在3 - 5周时就出现自发进行性肾病综合征，并伴有肥胖、高血压、低白蛋白血症、高胆固醇血症和高脂血症。对其肾脏进行的初步形态学和免疫荧光研究显示，肾小球逐渐出现节段性硬化病变，IgM在系膜区显著沉积，这一情况类似于人类类固醇抵抗型特发性肾病综合征，即局灶性肾小球硬化。
