Rangan G K, Wang Y, Harris D C
Renal Unit, Fremantle Hospital, Fremantle, Australia.
Contemp Top Lab Anim Sci. 2001 Sep;40(5):44-9.
Adriamycin nephropathy (AN) is a widely used nonimmune-mediated rat model of proteinuric chronic glomerular disease and is usually induced by a single intravenous injection of doxorubicin hydrochloride (DX) into the tail vein. However, this route can be associated with local skin necrosis and variability in disease induction and poses an occupational hazard to the investigator. Here we describe a simple technique of administering DX (1.7 mg) to ketamine:xylazine-sedated adult male Wistar rats (mean +/- 1 standard deviation, 238 +/- 8 g; n = 28) by using a single substernal intracardiac injection. The procedure was associated with minimal morbidity and mortality (1 death related to anesthesia). By day 21, severe nephrotic syndrome with effacement of glomerular epithelial cell foot processes and diffuse cortical tubulointerstitial injury was induced in all animals. Therefore, intracardiac injection of DX is a safe and consistent method of inducing AN in the rat and provides an alternative to the tail-vein route.
阿霉素肾病(AN)是一种广泛应用的蛋白尿性慢性肾小球疾病非免疫介导大鼠模型,通常通过单次尾静脉注射盐酸阿霉素(DX)诱导而成。然而,这种给药途径可能会导致局部皮肤坏死、疾病诱导的变异性,并且会给研究者带来职业危害。在此,我们描述一种简单的技术,即对用氯胺酮:赛拉嗪麻醉的成年雄性Wistar大鼠(平均±1个标准差,238±8 g;n = 28)通过单次胸骨内心脏注射给予DX(1.7 mg)。该操作导致的发病率和死亡率极低(1例死亡与麻醉有关)。到第21天,所有动物均诱发了严重的肾病综合征,伴有肾小球上皮细胞足突消失和弥漫性皮质肾小管间质损伤。因此,心脏内注射DX是在大鼠中诱导AN的一种安全且一致的方法,为尾静脉途径提供了一种替代方法。