阿霉素肾病大鼠模型的评价研究

目的 探索阿霉素不同的给药剂量和注射次数对模型的影响，确定阿霉素肾病大鼠模型的最佳造模条件。方法 54只成年雄性SD大鼠随机分为对照及模型A、B、C、D、E、F 7组，对照组于造模第1天尾iv生理盐水；模型A、B、C组于造模第1天分别尾iv阿霉素5.5、6.0、6.5 mg/kg；分别于造模第1、8天，模型D组尾iv阿霉素4.0、2.0 mg/kg，模型E组尾iv阿霉素4.0、2.5 mg/kg，模型F组尾iv阿霉素4.0、3.5 mg/kg。观察注射阿霉素后大鼠的一般状态、体质量、摄食量；于造模第4周末麻醉并处死大鼠，生化自动分析仪检测尿白蛋白/尿肌酐比值（ACR）、血清生化指标；HE染色观察肾脏组织形态学改变。结果 造模后，模型组大部分出现脱毛、腹泻、摄食量减少、体质量增长缓慢等症状。与对照组比较，各模型组于给药第1周ACR开始升高，且模型C、E、F组明显高于对照组（P<0.01），单次造模组于第3周达峰，并于造模第4周开始出现不同程度的回调，而分次模型组呈现出持续稳定增长，于第4周达峰。除F组尿素氮（BUN）高于对照组外，各模型组BUN、肌酐（CREA）、总蛋白（TP）、白蛋白（ALB）均有不同程度降低；大部分模型组总胆固醇（TC）和三酰甘油（TG）明显高于对照组（P<0.05、0.01）。病理切片显示，各模型组肾小球和肾小管出现不同程度损伤，且随造模剂量上升病变加重。结论 经改良间隔1周2次重复尾iv阿霉素可以高效、成功地建立阿霉素肾病大鼠模型，较其他造模组肾功能及病理改变更为典型、稳定，效果更佳。

Evaluation research of adriamycin-induced nephropathy model in rats

Objective To explore the effects of different doses and times of adriamycin on the models, and confirm the optimums of establishing adriamycin-induced nephropathy rat models. Methods Totally Fifty-four male healthy SD rats were randomly divided into 7 groups: control group, model A, B, C, D, E and F group. After adriamycin injection, the general status, body weight, food consumption, urinary albumin to creatinine ratio (ACR), serum biochemical indexes, and renal morphological changes were observed. Results After modeling, model groups obtained trichomadesis, diarrhea, lower food consumption and slower body weight. Compared with the control group, the urinary ACR in model groups were increased at first week, and ACR in the model C, E and F groups were significantly higher than those in the control groups (P < 0.01). The models by one injection reached the peak at the third week, and there were different levels of callback at the fourth week, the models by repeating injection showed the continuous and stable growth and reached the peak at the fourth week. Expect that Urea nitrogen (BUN) in the model F group was higher than control group, BUN, creatinine (CREA), total protein (TP), albumin (ALB) in each model group were decreased in varying degrees, TC and TG level in most model groups were significantly higher than those in the control group (P < 0.05, 0.01), total cholesterol (TC) and triacylglycerol (TG) were lower. Morphological slice displayed the glomerular and tubular were damaged to different degrees, the lesion severity of the model group was aggravated with increasing dose. Conclusion Adriamycin-induced nephropathy rat models can be effectively and successfully reproduced through repeating injection adriamycin twice a week at an improved interval, the model was more typical and stable change than other groups.