阿霉素诱导小鼠局灶节段性肾小球硬化肾病模型的研究

Adriamycin induced a nephropathy model of focal segmental glomerulosclerosis in mice

目的观察阿霉素诱导小鼠局灶节段性肾小球硬化发生的过程,为未来研究奠定基础。方法给BALB/c小鼠尾静脉一次性注射阿霉素,按10 mg/kg给予,动态观察阿霉素注射后1、2、4、6周尿蛋白、血生化及光镜、电镜下肾组织病理改变。结果从第1周开始尿蛋白增加,第2周达高峰,4、6周与2周相比稍有下降;血清白蛋白(ALB)于第1周开始下降(P<0.01),2周达最低值,4、6周较2周稍升高。光镜下,第1周肾小球无明显变化,肾小管可见蛋白管型;第2周部分肾小球可见节段性硬化,肾小管蛋白管型增多,较易见到;第4、6周可见50%以上肾小球中出现节段性硬化,肾小管扩张明显,可见大量蛋白管型及局部间质纤维化。电镜下,第1周偶可见足突融合,第2周足突融合更广泛,第4、6周出现足突融合变形,体积变大,胞质中微丝增多,并出现囊泡及包涵体,毛细血管袢闭塞,充血,大量红细胞填塞,内皮细胞孔消失,基底膜正常。结论单次BALB/c小鼠鼠尾静脉注射10 mg/kg阿霉素,可成功诱导局灶节段性肾小球硬化模型。

Objective As a pilot experiment for the future research,the aim of this study was to investigate the process of adriamycin-induced （ADR-induced） focal segmental glomerulosclerosis （FSGS） in mice.Methods The nephropathy model of FSGS was induced in BALB/c mice by tail vein injection of ADR（10 mg/kg）.Urine protein,biochemical tests,pathological leisions under light microscope（LM） and electronic microscope（EM） were observed at 1 st,2 nd,4 th and 6 th week after the injection.Results Urine protein increased from 1 st week after injection,and reached the peak at 2 nd week after injection.Meanwhile,serum albumin （ALB）decreased from 1 st week after the injection,and reached the lowest level at the 2 nd week.Under LM study,no change was found in glomerulus at 1st week after injection though protein cast was demonstrated.Segmental sclerosis in more than 50％ glomeruli and obvious tubular expansion were observed at 2 nd and 4 th week after the injection,and protein cast and interstitial fibrosis were testified as well.Under EM study,fusion of podocyte foot processes was demonstrated at 1 st week after injection,and the change became more extensive at 2 nd week after the injection.After 4 th or 6 th week,the fusion of the foot processes and morphological changes were observed.Enlargement of the cell,increase of microfilament in cytoplasm and appearance of the vesicle or inclusion body were also demonstrated.Capsular loops were blocked by large amount of red blood cells and endothelial cell hole vanished,while normal structure of basement membrane was demonstrated.Conclusion FSGS model in BALB/c mice can be successfully induced by a single tail vein injection of adriamycin at the dose of 10 mg/kg body weight.