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Development of Spontaneous nephotic rats and Their Pathological characteristics

自发性肾病大鼠的发育及其病理学特征

基本信息

批准号：
59870017
负责人：
YAMORI Yukio
金额：
$ 4.42万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1986
项目状态：
已结题

项目摘要

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".

由于没有合适的大鼠模型，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个近交系大鼠中选择性近亲繁殖具有中度蛋白尿的OM大鼠。由此建立的OM大鼠在生命早期出现明显的蛋白尿，其随着衰老过程逐渐进展，直至超过200 mg/天的严重蛋白尿。这些大鼠显示双侧肾脏增大，光学显微镜下显示肾小球系膜细胞轻微增生性变化和近端小管扩张伴透明圆柱体，电子显微镜下与微小病变肾病综合征中的轻微肾小球异常一致。这些模型进一步用类固醇激素（Predonisolon 3 mg/kg，p.o.）但蛋白尿只是暂时减轻，总体上是抵抗性的。为了建立肾病高血压肾损害模型，将这些OM株与易卒中SHR（stroke-prone SHR，SHRSP）杂交，<F_1>获得中度蛋白尿和轻度高血压的杂种。从杂交育种中<F_1>，<F_2>获得了后代，并进一步培育了<F_2>具有中度高血压和显著蛋白尿的分离世代的后代。选择性饲养的OM大鼠和OM与SHRSP杂交获得的SPOM大鼠可作为“成人型激素抵抗型微小病变肾病”的新模型。