Department of Urology, Paediatric Urology Research Center, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran 1998714616, Iran.
J Pediatr Surg. 2011 Aug;46(8):1544-9. doi: 10.1016/j.jpedsurg.2011.04.015.
The Adriamycin rat model is an established model for different organ anomalies including congenital obstructive uropathy. In the current study, we carried out a dose-response analysis to find out the optimal dose of Adriamycin to create a viable rat model of obstructive uropathy.
Thirty time-mated Sprague-Dawley rats were divided into 5 groups including 1 control group and 4 different treatment groups. The 4 Adriamycin dosage regimens investigated in this study were 1.25, 1.5, 1.75, and 2 mg/(kg d). Experimental rats (n = 24) were injected intraperitoneally with different doses of Adriamycin on gestational days 7 to 9 (6 rats in each group). Control rats (n = 6) were injected with an equivalent volume of saline on the same days. Viable term fetuses were harvested on gestational day 21 by cesarean delivery and dissected under a dissecting microscope. Serial transverse sections from urinary tract system were obtained for histological examination.
One hundred thirty-three viable fetuses were recovered from Adriamycin-treated rats, and 50 were from rats in the control group. There were no resorptions in the control group; however, 52 resorptions were recorded in Adriamycin groups. The rates of hydronephrosis and resorptions were 60% and 0%, 80.5% and 5.8%, 100% and 17.3%, and 100% and 76.9% at doses of 1.25, 1.50, 1.75, and 2 mg/(kg d), respectively. Histologic examination of the kidneys in the treated groups showed a significant decrease in renal parenchyma compared with the control group.
The dosage of 1.5 mg/(kg d) of Adriamycin yielded the highest number of viable hydronephrotic fetuses. At this dose, urinary abnormalities are milder; but the highest number of viable fetuses is provided, which is necessary to create a reproducible and viable animal model.
阿霉素大鼠模型是一种已建立的模型，可用于研究包括先天性尿路梗阻在内的多种器官异常。在本研究中，我们进行了剂量反应分析，以确定创建梗阻性尿路病变可行大鼠模型的最佳阿霉素剂量。
30 只同期交配的 Sprague-Dawley 大鼠分为 5 组，包括 1 个对照组和 4 个不同的治疗组。本研究共研究了 4 种不同的阿霉素剂量方案，分别为 1.25、1.5、1.75 和 2mg/（kg·d）。实验大鼠（n=24）于妊娠第 7 至 9 天（每组 6 只）经腹腔注射不同剂量的阿霉素。对照组大鼠（n=6）于相同日期注射等量生理盐水。通过剖宫产术收获妊娠第 21 天的活产胎儿，并在解剖显微镜下进行解剖。从泌尿系统中获得连续的横切片进行组织学检查。
从阿霉素处理的大鼠中回收了 133 个活产胎儿，从对照组大鼠中回收了 50 个。对照组无胎儿吸收；然而，阿霉素组记录了 52 个胎儿吸收。在剂量为 1.25、1.50、1.75 和 2mg/（kg·d）时，肾盂积水和胎儿吸收的发生率分别为 60%和 0%、80.5%和 5.8%、100%和 17.3%以及 100%和 76.9%。治疗组肾脏的组织学检查显示与对照组相比，肾实质明显减少。
1.5mg/（kg·d）阿霉素剂量可获得最多的活产肾盂积水胎儿。在这个剂量下，尿路异常较轻；但提供了最多的活产胎儿，这是创建可重复和可行的动物模型所必需的。
