Development of Spontaneous nephotic rats and Their Pathological characteristics

由于目前尚无合适的大鼠模型，我们试图从美国国立卫生研究院从世界各地不同实验室收集的30个近交系大鼠中发现中度蛋白尿的OM大鼠进行选择性近亲繁殖。这样建立的OM大鼠在生命早期就会出现明显的蛋白尿，随着年龄的增长逐渐加重，直到每天超过200毫克的严重蛋白尿。大鼠双侧肾脏肿大，光镜下可见肾小球系膜细胞轻度增殖性改变，近端肾小管呈透明柱状扩张，光镜下可见微小病变型肾病综合征肾小球轻度异常。这些模型进一步给予类固醇激素(强的松龙3 mg/kg，P.O.)治疗。但蛋白尿只是暂时性的减弱，总体上相当抵抗。为了建立肾病合并高血压肾损害模型，将这些OM株与卒中易感型自发性高血压(SHRSP)杂交，获得中度蛋白尿和轻度高血压的&lt；F1&gt；杂交种。通过&lt；F_1&gt；杂交获得了&lt；F_2&gt；后代，并育成了具有中度高血压和明显蛋白尿的&lt；F_2&gt；分离世代的后代。这些由OM和SHRSP杂交获得的选择性繁殖的OM大鼠和SPOM大鼠被认为是“成人型激素抵抗型微小病变型肾病”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".