三种大鼠肾小管间质损伤模型的比较实验研究

目的　比较三种大鼠肾小管间质损伤模型。方法　采用庆大霉素腹腔注射、单侧输尿管梗阻、环孢素A(CsA)灌胃三种不同的方法 ,损伤大鼠的肾小管间质 ,测定尿液、血液各项生化指标 ,观察肾脏病理改变情况。结果　与对照组比较 ,三种模型的肾脏指数均明显增加 ,差异有极显著性 (P <0 0 1) ;庆大霉素模型尿蛋白和NAG酶在 7d时急剧增高 ,而在 15d时NAG酶差异已无显著性 ,单侧输尿管梗阻模型尿蛋白和NAG酶均显著增高 ,CsA模型的尿蛋白则呈下降趋势 ( 7dP <0 .0 5 ,15dP <0 0 1) ;三种模型的血清SCR、BUN均显著升高 ,TP、ALB均显著下降 ,15d时庆大霉素模型和单侧输尿管梗阻模型差异无显著性。镜下可见 :三种模型的肾间质均可见炎性细胞浸润 ,肾小管明显扩张 ,上皮空泡变性 ,仅单侧输尿管梗阻模型的间质趋向纤维化 ,CsA模型的病变相对轻微。结论　三种方法均可造成大鼠不同程度的肾小管间质损伤 ,单侧输尿管梗阻模型的肾小管间质纤维化病变明显 ,与临床肾脏病的表现相似 ,是一个较为理想可行的肾小管间质损伤模型 ,而庆大霉素模型 7d即能严重损伤肾小管间质 ,可作为急性的肾小管间质损伤模型 ,CsA模型则不如庆大霉素模型与单侧输尿管梗阻模型理想。

Study on Renal Tubulointerstitial Injury Model in Rats

Objective To compare the three models of renal tubulointerstitial injury. Methods Gentamycin ip.(GM), unilateral ureteral obstruction(UUO), cyclosporine A(CsA) fed by oral were used to make the renal tubulointerstitial injury, then to detect urine biochemistry and blood biochemistry, and observe nephritic pathology. Results The nephridium indices of the models were all significantly higher in comparion with the control group(%p%<0^01). Urine protein and NAG enzyme of the GM model were significantly higher than the control on the 7th day, however, no significant difference was observed on the 15th day. Urine protein and NAG enzyme of the UUO model were significantly higher than the control on the 7th and 15th day, whereas urine protein of the CsA model was lower (7d %p%<0.05, 15d %p%<0.01). SCR and BUN of the three models were significantly higher than the control, whereas TP and ALB of the three models were significant lower than the control, There's no significant difference between the GM model and the UUO model on 15th day. Observation under light microscope showed inflammatory cell in interstitium, outspread of renal tubules, fibrosis in interstituium of the UUO model. The morphological changes were much slighter in the CsA model. Conclusion The three methods all could cause different level of renal tubulointerstitial injury. Fibrosis in interstitium of the UUO model was like the sign of clinical nepherosis. The UUO model was an ideal model for the study of the renal tubulointerstitial injury. The GM model seriously generating renal tubulointerstitial injury on the 7th day could be used for the acute model. However, the CsA model was not equal to the GM and the UUO models.;