Guerin Florent, Azoulay Robin, Berrebi Dominique, Sebag Guy, Aigrain Yves, Peuchmaur Michel, El-Ghoneimi Alaa
Department of Pediatric Surgery and Urology, Hôpital Robert Debré, APHP, University of Paris VII, René Diderot, Paris, France.
J Urol. 2008 Apr;179(4):1553-63. doi: 10.1016/j.juro.2007.11.088. Epub 2008 Mar 4.
The mechanism underlying the evolution of congenital obstructive hydronephrosis in humans is still unclear. Although partial unilateral ureteral obstruction has been extensively explored in rats, studies in neonatal mice may lead to new insights into underlying cellular mechanisms, especially with the availability of mutant mice. We developed a model of partial unilateral ureteral obstruction in newborn mice.
Mice were operated on by the fifth day of life. We created 3 groups, namely partial unilateral ureteral obstruction (embedding the ureter in the psoas muscle), complete unilateral ureteral obstruction (ligating the ureter) and sham (exposing the ureter). We studied pelvis diameter and kidney length on magnetic resonance imaging, and kidney weight, inflammation, apoptosis and fibrosis on histological assessment during the second (early) and fourth weeks (late) postoperatively.
Magnetic resonance imaging showed enlarged pelvis diameter in late partial unilateral ureteral obstruction, and in early and late complete unilateral ureteral obstruction. Pathological studies revealed parenchyma atrophy in early and late partial unilateral ureteral obstruction. Apoptosis occurred early in partial unilateral ureteral obstruction and decreased later. Macrophage infiltration was enhanced in early and late partial unilateral ureteral obstruction. Fibrosis increased in late partial unilateral ureteral obstruction. All of these results were significantly intermediate between mice with complete unilateral ureteral obstruction and sham operated mice.
It is possible to create renal lesions in newborn mice specific to partial ureteral obstruction. Magnetic resonance imaging of morphological changes demonstrated specific features of partial unilateral ureteral obstruction. Being noninvasive, this approach opens the way for further studies to investigate prognostic parameters after partial ureteral obstruction. In the future this model could be used in knockout mice to study the pathogenesis of renal lesions secondary to obstruction.
人类先天性梗阻性肾盂积水的演变机制仍不清楚。尽管大鼠单侧输尿管部分梗阻已得到广泛研究，但对新生小鼠的研究可能会为潜在的细胞机制带来新的见解，尤其是在有突变小鼠可用的情况下。我们建立了新生小鼠单侧输尿管部分梗阻模型。
在小鼠出生后第5天进行手术。我们创建了3组，即单侧输尿管部分梗阻组（将输尿管埋入腰大肌）、单侧输尿管完全梗阻组（结扎输尿管）和假手术组（暴露输尿管）。我们在术后第2周（早期）和第4周（晚期）通过磁共振成像研究肾盂直径和肾脏长度，并通过组织学评估研究肾脏重量、炎症、细胞凋亡和纤维化情况。
磁共振成像显示，晚期单侧输尿管部分梗阻以及早期和晚期单侧输尿管完全梗阻时肾盂直径增大。病理研究显示，早期和晚期单侧输尿管部分梗阻时实质萎缩。单侧输尿管部分梗阻早期发生细胞凋亡，后期减少。早期和晚期单侧输尿管部分梗阻时巨噬细胞浸润增强。晚期单侧输尿管部分梗阻时纤维化增加。所有这些结果在单侧输尿管完全梗阻小鼠和假手术小鼠之间均显著处于中间状态。
有可能在新生小鼠中造成特定于输尿管部分梗阻的肾脏病变。形态学变化的磁共振成像显示了单侧输尿管部分梗阻的特定特征。这种非侵入性方法为进一步研究输尿管部分梗阻后的预后参数开辟了道路。未来，该模型可用于基因敲除小鼠，以研究梗阻继发肾脏病变的发病机制。
