目的 探索阿霉素不同的給藥劑量和注射次數(shù)對模型的影響，確定阿霉素腎病大鼠模型的最佳造模條件。方法 54只成年雄性SD大鼠隨機分為對照及模型A、B、C、D、E、F 7組，對照組于造模第1天尾iv生理鹽水；模型A、B、C組于造模第1天分別尾iv阿霉素5.5、6.0、6.5 mg/kg；分別于造模第1、8天，模型D組尾iv阿霉素4.0、2.0 mg/kg，模型E組尾iv阿霉素4.0、2.5 mg/kg，模型F組尾iv阿霉素4.0、3.5 mg/kg。觀察注射阿霉素后大鼠的一般狀態(tài)、體質量、攝食量；于造模第4周末麻醉并處死大鼠，生化自動分析儀檢測尿白蛋白/尿肌酐比值（ACR）、血清生化指標；HE染色觀察腎臟組織形態(tài)學改變。結果 造模后，模型組大部分出現(xiàn)脫毛、腹瀉、攝食量減少、體質量增長緩慢等癥狀。與對照組比較，各模型組于給藥第1周ACR開始升高，且模型C、E、F組明顯高于對照組（P<0.01），單次造模組于第3周達峰，并于造模第4周開始出現(xiàn)不同程度的回調，而分次模型組呈現(xiàn)出持續(xù)穩(wěn)定增長，于第4周達峰。除F組尿素氮（BUN）高于對照組外，各模型組BUN、肌酐（CREA）、總蛋白（TP）、白蛋白（ALB）均有不同程度降低；大部分模型組總膽固醇（TC）和三酰甘油（TG）明顯高于對照組（P<0.05、0.01）。病理切片顯示，各模型組腎小球和腎小管出現(xiàn)不同程度損傷，且隨造模劑量上升病變加重。結論 經改良間隔1周2次重復尾iv阿霉素可以高效、成功地建立阿霉素腎病大鼠模型，較其他造模組腎功能及病理改變更為典型、穩(wěn)定，效果更佳。

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.

R965.1

國家科技重大新藥創(chuàng)制項目（2015ZX09501004）