Wang Guixian, Topcu Sukru Oguzkan, Ring Troels, Wen Jianguo, Djurhuus Jens Christian, Kwon Tae-Hwan, Nielsen Søren, Frøkiaer Jørgen
The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark.
Pediatr Nephrol. 2009 Aug;24(8):1487-500. doi: 10.1007/s00467-009-1193-y. Epub 2009 Jun 3.
Congenital obstructive nephropathy accounts for a major proportion of renal insufficiency in infancy and childhood. In an earlier investigation we demonstrated that bilateral complete ureteral obstruction (BUO) in rats is associated with inadequate urinary acidification [Am J Physiol Renal Physiol. 295(2):F497-506, 2008]. The aim of the study reported here was to determine whether this defect is also associated with unilateral ureteral obstruction (UUO), which is clinically more common than BUO. The time-course of the changes in protein expression levels of major renal acid-base transporters was examined at 7 and 14 weeks in rats with neonatally induced partial unilateral ureteral obstruction (PUUO), which was performed within the first 48 h of life. We observed that protein expression of the renal acid-base transporters NHE3, NBC1, NBCn1, pendrin and Na(+)-K(+)-ATPase was increased in both obstructed and non-obstructed kidneys 7 weeks after the induction of neonatal PUUO. This was confirmed by immunocytochemistry. In contrast, 14 weeks after the induction of PUUO, there was a significant downregulation of the renal acid-base transporters NBC1, NBCn1 and Na(+)-K(+)-ATPase in the obstructed kidneys. These time/age-dependent changes in protein expression were associated with parallel changes in renal function resulting in urine acidification in response to exogenous acid loading. In conclusion, these results show that downregulation of protein expression is a time/age-dependent response to PUUO, which could contribute to the decreased net acid excretion and development of metabolic acidosis in neonatal rats with PUUO.
先天性梗阻性肾病在婴儿期和儿童期肾功能不全中占很大比例。在早期的一项研究中，我们证明大鼠双侧完全输尿管梗阻（BUO）与尿液酸化不足有关[《美国生理学杂志：肾脏生理学》。295(2):F497 - 506, 2008]。本文报道的研究目的是确定这种缺陷是否也与单侧输尿管梗阻（UUO）有关，UUO在临床上比BUO更常见。在出生后48小时内对新生大鼠进行部分单侧输尿管梗阻（PUUO），并在7周和14周时检查主要肾脏酸碱转运蛋白表达水平变化的时间进程。我们观察到，新生PUUO诱导7周后，梗阻和未梗阻肾脏中肾脏酸碱转运蛋白NHE3、NBC1、NBCn1、pendrin和Na(+)-K(+)-ATP酶的蛋白表达均增加。免疫细胞化学证实了这一点。相比之下，PUUO诱导14周后，梗阻肾脏中肾脏酸碱转运蛋白NBC1、NBCn1和Na(+)-K(+)-ATP酶显著下调。这些蛋白表达的时间/年龄依赖性变化与肾功能的平行变化相关，导致对外源性酸负荷的尿液酸化。总之，这些结果表明蛋白表达下调是对PUUO的时间/年龄依赖性反应，这可能导致新生PUUO大鼠净酸排泄减少和代谢性酸中毒的发生。
