Development of Spontaneous nephotic rats and Their Pathological characteristics

由于没有合适的大鼠模型，我们试图对美国国立卫生研究院从世界不同实验室收集的30个自交系大鼠中发现的中度蛋白尿的OM大鼠进行选择性近交系繁殖。因此，OM大鼠在生命早期就出现了明显的蛋白尿，随着年龄的增长，这种情况逐渐加剧，直到严重的蛋白尿超过200毫克/天。大鼠双侧肾脏肿大，光镜下肾小球系膜细胞增生，近端小管扩张，呈玻璃样柱状，电镜下与微小变化肾病综合征肾小球轻微异常一致。这些模型进一步用类固醇激素（强的松3mg /kg， p.o）治疗，但蛋白尿只是暂时减轻，而且总体上相当耐药。为了建立肾病和高血压肾损害模型，将这些OM菌株与卒中易感SHR （SHRSP）杂交，获得<F_1>、中度蛋白尿和轻度高血压的杂交鼠。通过<F_1>的杂交，得到<F_2>的后代，并进一步培育出<F_2>分离代的后代，具有中度高血压和明显的蛋白尿。这些选择性繁殖的OM大鼠和OM与SHRSP杂交获得的SPOM大鼠被认为是“成体类固醇抵抗性微小变化肾病”的新模型。

Since there had been no appropriate rat models for naphrosis, we attempted to start selective inbreeding of OM rats with moderate proteinuria which were found among 30 inbred rat strains collected through National Institutes of Health, U.S.A. from different laboratories in the world. The OM rats, thus established develop a marked proteinuria early in life which is progressively advanced by ageing process up to the severe proteinuria over 200 mg/day. These rats show bilateral enlargement of kidneys which light microscopically show a slight proliferative change of mesangial cells of glomeruli and dilatation of proximal tubuli with hyaline cylinders, and electronmicroscopically are consistent with minor glomerular abnormalities in minimal change nephrotic syndrome. These models were further treated with steroid hormone (Predonisolon 3 mg/kg, p.o.) but proteinuria was attenuated only temporally and rather resistant in general. In order to establishe a model with nephrotic and hypertensive renal lesions, these OM strains were cross-bred with stroke-prone SHR (SHRSP) to obtain <F_1> hybrid with moderate proteinuria and mild hypertension. From the cross breeding among <F_1> , <F_2> offsprings were obtained and further the offspring of <F_2> segregate generation with moderate hypertension and a marked proteinuria has been bred. These selectively bred OM rats and SPOM rats obtained by cross breeding between OM and SHRSP are regarded as new models for "adult type steroid resistant minimal change nephrosis".