单次静脉注射嘌呤霉素氨基核苷所致大鼠肾病模型的优化及评价  

Optimization and Evaluation of Puromycin Aaminonucleoside Nephropathy Model in Rats

作　　者：刘丽华[1] 朱春芳[2] 欧周罗[2] 

机构地区：[1]绍兴文理学院医学院生物化学教研室,绍兴312000 [2]复旦大学上海医学院生物化学与分子生物学系,上海200032

出　　处：《复旦学报（医学版）》2005年第4期488-492,共5页Fudan University Journal of Medical Sciences

摘　　要：目的明确大鼠嘌呤霉素氨基核苷(puromycin aminonucleoside,PAN)肾病模型的适宜条件和病程演变,为该模型更好地用于肾病综合征、肾硬化发病机制及治疗的研究奠定基础.方法用6周龄雄性Wistar大鼠,一次性颈静脉注射PAN,分别以2、3、4、5、7、9 mg/100 g体重的剂量给药,以等量生理盐水作对照,测定2周内不同时间点的尿蛋白排泄量;另以9 mg/100 g体重的剂量给药,观察28周内尿蛋白、血清胆固醇和三酰甘油的变化及肾组织的病理改变.结果各个剂量的PAN均可引起不同程度的蛋白尿,约在10～14 d达到高峰,最高达(592.0±61.0)mg/24 h.28周连续观察的结果显示,PAN组动物的尿蛋白呈现典型的双相曲线,即第2周达到高峰,伴有血清胆固醇及三酰甘油的升高,此后逐渐降至接近正常,但自第12周起尿蛋白再度逐渐上升,第28周可达急性期峰值的一半.结论6周龄雄性Wistar大鼠,一次性颈静脉注射适量PAN可建立不同程度的肾病模型,成功率极高,方法简单,用药量省,动物价廉易得,且急性期发病快而周期短,不失为研究人类相应疾病的良好模型.Purpose This study was aimed at finding the optimal conditions for producing both acute and chronic renal lesions in rat by puromycin aminonucleoside (PAN),for illustrating the mechanism of minimal change nephrotic syndrome (MCNS) and focal segmental glomeruloscleorosis (FSGS). Methods Male Wistar rats received a single intravenous injection of PAN at dose of 2,3,4,5,7 or 9 mg/100 g body weight via the left internal jugular vein,for optimizing MCNS model.In addition,two groups of rats treated with or without PAN were fed for 28 weeks,for establishing FSGS model.The time course of urinary protein,urinary albumin,serum cholesterol,serum triglyceride,glomerular and interstitial changes were monitored. Results All of dosage of PAN except for 2 mg/100 g body weight induced massive urinary protein with hyperlipidemia.Urinary protein increased from day 5,and the peak was around day 10 after PAN administration.A typical diphasic curve of urinary protein excretion could be observed,i.e. after the acute phase,urinary protein excretion declined nearly to the normal levels from 2nd week and persisted for 10 weeks,and then gradually increased from 12th week up to 28 weeks,accompanying with FSGS and interstitial fibrosis. Conclusions Renal lesion induced by a single intravenous injection of PAN at suitable dosage in 6-weeks old Wistar rats is a good model for studying both acute nephrotic syndrome and chronic FSGS.

关 键 词：肾病模型 嘌呤霉素氨基核苷 单次静脉注射 Wistar大鼠 血清胆固醇 优化 尿蛋白排泄量 三酰甘油 不同程度 肾病综合征 PAN 病程演变 发病机制 生理盐水 不同时间 病理改变 连续观察 一次性 急性期 肾硬化 剂量 肾组织 蛋白尿 

分 类 号：R692.6[医药卫生—泌尿科学] R977.11[医药卫生—外科学]