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A study on establishment of a renal toxicity model using nephretomized rats

肾切除大鼠肾毒性模型的建立研究

基本信息

批准号：
08660393
负责人：
YOSHIDA Midori
金额：
$ 1.6万
依托单位：
Sasaki Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

To establish a renal toxicity model using 5/6 nephretomized rats, changes of biochemical parameters and histological findings were sequentially investigated in 5/6 nephrectomized rats. Changes of creatinine clearance and electrolyte reabsorption, indicatorsforglomerular and tubaular functions, respectively, were divided into three stages : a reduction at weeks 2 to 4after nephrectomy, a slight increase from weeks 6 to 10, and a reduction again thereafter. These changes were considered to be correlated to alteration of renal function after nephrectomy : the early stage indicating acute renal failure caused by marked decrease of nephron units, the middle one showing physiological compensatory adaptation, and the late one being attributed to an onset of chromic renal failure, respectively. These results indicate that clinical biochemical parameters such as creatinine clearance and electolyte reabsorption are good indicators fo distinguish three stages of renal dysfunction in 5/6 nephrectomized rats. In addition, morphological canges were also divided similarly into same stages.To examine the effect of renal toxicants in nephrectomized rats, gentamycin and puromycin were tested. Gentamycin-induced tubular lesions worsened biochemically and morphologically in the nephrectomized rats treated when gentamycin was given at the early, middle or late stages, especially in the middle stage compared with those in the sham operated rats. In contrast, the increase in glomerular toxicity was only detectable in nephrectomized rats by biochemical indicators when low-dose puromycin wasgiven at the middle stage. The result suggests that some biochemical parameters may be morae sensitivethan morphological examinaation to detect glomerular toxicity.In conclusion, our study described above suggests that the 5/6 nephrecomized rat is a useful model for detection of renal toxicity and that the middle stage is a more effective time to detect it.

为建立5/6肾切除大鼠肾毒性模型，对5/6肾切除大鼠的生化指标和组织学改变进行了观察。肾切除后2 ~ 4周肌酐清除率和电解质重吸收率下降，6 ~ 10周略有上升，此后又下降。这些变化被认为与肾切除术后肾功能的改变有关：早期表明肾单位明显减少而引起的急性肾衰竭，中期表明生理性代偿适应，晚期则归因于慢性肾衰竭的发生。结果表明，临床生化指标如肌酐清除率和电解质重吸收是区分5/6肾切除大鼠肾功能不全三个阶段的良好指标。此外，形态学改变也同样分为相同的阶段。为了检查肾毒物对肾切除大鼠的影响，进行了庆大霉素和嘌呤霉素的试验。与假手术组相比，肾切除大鼠在早期、中期和晚期给予庆大霉素后，其肾小管损伤在生化和形态学上均加重，尤以中期更为明显。相反，只有在中期给予小剂量嘌呤霉素时，肾切除大鼠的生化指标才能检测到肾小球毒性的增加。结果提示，某些生化指标比形态学检查更敏感，提示5/6肾切除大鼠是一种较好的肾毒性检测模型，中期是较好的检测时机。