Hesketh Emily E, Vernon Madeleine A, Ding Peng, Clay Spike, Borthwick Gary, Conway Bryan, Hughes Jeremy
MRC Centre for Inflammation Research, University of Edinburgh.
MRC Centre for Inflammation Research, University of Edinburgh;
J Vis Exp. 2014 Dec 20(94):52559. doi: 10.3791/52559.
Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive nephropathy induced by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). In the irreversible UUO model, the ureter may be obstructed for variable periods of time in order to induce increasingly severe renal inflammation and interstitial fibrotic scarring. In the reversible R-UUO model the ureter is obstructed to induce hydronephrosis, tubular dilation and inflammation. After a suitable period of time the ureteric obstruction is then surgically reversed by anastomosis of the severed previously obstructed ureter to the bladder in order to allow complete decompression of the kidney and restoration of urinary flow to the bladder. The irreversible UUO model has been used to investigate various aspects of renal inflammation and scarring including the pathogenesis of disease and the testing of potential anti-inflammatory or anti-fibrotic therapies. The more challenging model of R-UUO has been used by some investigators and does offer significant research potential as it allows the study of inflammatory and immune processes and tissue remodeling in an injured and scarred kidney following the removal of the injurious stimulus. As a result, the R-UUO model offers investigators the opportunity to explore the resolution of kidney inflammation together with key aspects of tissue repair. These experimental models are of relevance to human disease as patients often present with obstruction of the renal tract that requires decompression and are commonly left with significant residual kidney impairment that has no current treatment options and may lead to eventual end stage kidney failure.
肾脏梗阻可能影响自体肾或移植肾,导致肾损伤和瘢痕形成。本文介绍一种由单侧输尿管梗阻(UUO)诱导的梗阻性肾病模型,该模型可以是不可逆的(UUO),也可以是可逆的(R-UUO)。在不可逆UUO模型中,输尿管可被梗阻不同时间段,以诱导越来越严重的肾脏炎症和间质纤维化瘢痕形成。在可逆R-UUO模型中,输尿管被梗阻以诱导肾积水、肾小管扩张和炎症。经过适当时间后,通过将先前梗阻的输尿管断端与膀胱吻合进行手术解除输尿管梗阻,以使肾脏完全减压并恢复尿液向膀胱的流动。不可逆UUO模型已被用于研究肾脏炎症和瘢痕形成的各个方面,包括疾病的发病机制以及潜在抗纤维化治疗的测试。一些研究者使用了更具挑战性的R-UUO模型,该模型确实具有显著的研究潜力,因为它允许在去除损伤性刺激后,研究受损和瘢痕化肾脏中的炎症和免疫过程以及组织重塑。因此,R-UUO模型为研究者提供了探索肾脏炎症消退以及组织修复关键方面的机会。这些实验模型与人类疾病相关,因为患者常出现需要减压的尿路梗阻,并且通常会留下严重的残余肾功能损害,目前没有治疗选择,可能最终导致终末期肾衰竭。