Shi Yimin, Pedersen Michael, Li Chunling, Wen Jian Guo, Thomsen Klaus, Stødkilde-Jørgensen Hans, Jørgensen Troels Munch, Knepper Mark A, Nielsen Søren, Djurhuus Jens Christian, Frøkiaer Jørgen
The Water and Salt Research Center, Institute of Experimental Clinical Research, Aarhus Univ. Hospital-Skejby, DK-8200 Aarhus, Denmark.
Am J Physiol Renal Physiol. 2004 Jun;286(6):F1087-99. doi: 10.1152/ajprenal.00201.2003. Epub 2004 Jan 13.
The incidence of congenital hydronephrosis is approximately 1% and is often associated with renal insufficiency. It is unknown whether early release is essential to prevent deterioration of renal function. Rats were subjected to partial unilateral ureteral obstruction (PUUO) on postnatal day 2. The obstruction was left in place or released after 1 or 4 wk. Renal blood flow (RBF) and kidney size were measured sequentially over 24 wk using MRI. In rats in which the obstruction was left in place, RBF of the obstructed kidney was progressively reduced to 0.92 +/- 0.17 vs. 1.79 +/- 0.12 ml.min(-1).100 g body wt(-1) (P < 0.05) after 24 wk. Similarly, glomerular filtration rate of the obstructed kidney was severely reduced at 24 wk: 172 +/- 36 vs. 306 +/- 42 microl.min(-1).100 g body wt(-1) (P < 0.05). These changes were preceded by development of severe hydronephrosis and obstructive nephropathy with a reduction in total protein content: 45 +/- 3 vs. 58 +/- 4 mg/kidney. Moreover, nonreleased PUUO caused a marked natriuresis (0.32 +/- 0.07 vs. 0.11 +/- 0.02 micromol.min(-1).100 g body wt(-1), P < 0.05) and impaired solute free water reabsorption (0.47 +/- 0.16 vs. 2.71 +/- 0.67 microl.min(-1).100 g body wt(-1), P < 0.05), consistent with a significant downregulation of Na-K-ATPase to 62 +/- 7%, aquaporin-1 to 53 +/- 3%, and aquaporin-3 to 53 +/- 7% of sham levels. Release after 1 wk completely prevented development of hydronephrosis, reduction in RBF and glomerular filtration rate, and downregulation of renal transport proteins, whereas release after 4 wk had no effect. These results suggest that early release of neonatal obstruction provides dramatically better protection of renal function than release of obstruction after the maturation process is completed.
先天性肾积水的发病率约为1%，且常与肾功能不全相关。早期解除梗阻对于预防肾功能恶化是否至关重要尚不清楚。在出生后第2天对大鼠进行部分单侧输尿管梗阻（PUUO）。梗阻维持原状或在1周或4周后解除。使用磁共振成像（MRI）在24周内连续测量肾血流量（RBF）和肾脏大小。在梗阻维持原状的大鼠中，24周后梗阻侧肾脏的RBF逐渐降至0.92±0.17，而假手术组为1.79±0.12 ml·min⁻¹·100 g体重⁻¹（P<0.05）。同样，梗阻侧肾脏的肾小球滤过率在24周时严重降低：172±36，而假手术组为306±42 μl·min⁻¹·100 g体重⁻¹（P<0.05）。这些变化之前伴有严重肾积水和梗阻性肾病的发展，总蛋白含量降低：45±3，而假手术组为58±4 mg/肾脏。此外，未解除的PUUO导致显著的利钠作用（0.32±0.07，而假手术组为0.11±0.02 μmol·min⁻¹·100 g体重⁻¹，P<0.05）以及溶质自由水重吸收受损（0.47±0.16，而假手术组为2.71±0.67 μl·min⁻¹·100 g体重⁻¹，P<0.05），这与钠钾ATP酶显著下调至假手术组水平的62±7%、水通道蛋白-1下调至53±3%以及水通道蛋白-3下调至53±7%一致。1周后解除梗阻完全预防了肾积水的发展、RBF和肾小球滤过率的降低以及肾转运蛋白的下调，而4周后解除梗阻则没有效果。这些结果表明，新生儿梗阻的早期解除比成熟过程完成后解除梗阻能显著更好地保护肾功能。
