Chung K H, Chevalier R L
Department of Urology, Gyeong-sang National University, Chinju, Korea.
J Urol. 1996 Mar;155(3):1139-44. doi: 10.1097/00005392-199603000-00095.
The purpose of this study was to investigate the role of growth-related peptides in the impairment of renal growth and development resulting from unilateral ureteral obstruction (UUO) in the neonatal rats.
Sprague-Dawley rats underwent UUO or sham-operation in the first 48-hours of life, and kidneys were harvested 1 to 28 days later. Renal messenger RNA (mRNA) was quantitated for renin, transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF). Renal interstitial volume was measured in Masson-trichrome-stained sections, and renin and alpha-smooth muscle actin (alpha-SM actin) distribution were determined by immunocytochemistry.
The normal developmental increase in renal mass and DNA content were suppressed in ipsilateral UUO and increased in the intact opposite kidney. Renal interstitial volume was increased more than 10-fold by ipsilateral UUO. Unilateral ureteral obstruction resulted in a sustained increased in ipsilateral renal renin mRNA and persistence of fetal renin distribution. Renin in the contralateral kidney was suppressed. Transforming growth factor-beta 1 expression increased progressively in the obstructed kidney, but decreased after 7 days in sham-operated kidneys. While renal EGF expression was undetectable in the normal sham kidney during the first 3 days of life, it increased steadily with maturation. However, EGF expression remained suppressed in the obstructed kidney. Whereas alpha-SM actin disappeared from the interstitium of normal rat kidneys by 15 days of age, it persisted in the obstructed neonatal kidney.
As revealed by changes in expression of growth-related peptides, neonatal UUO delays ipsilateral renal development, which may contribute to impaired renal growth.
本研究旨在探讨生长相关肽在新生大鼠单侧输尿管梗阻（UUO）所致肾脏生长发育受损中的作用。
将Sprague-Dawley大鼠在出生后的头48小时内进行单侧输尿管梗阻手术或假手术，1至28天后摘取肾脏。对肾脏中的肾素、转化生长因子-β1（TGF-β1）和表皮生长因子（EGF）的信使核糖核酸（mRNA）进行定量分析。在经Masson三色染色的切片中测量肾间质体积，并通过免疫细胞化学法确定肾素和α平滑肌肌动蛋白（α-SM肌动蛋白）的分布。
同侧输尿管梗阻抑制了肾脏质量和DNA含量的正常发育性增加，而完整的对侧肾脏则增加。同侧输尿管梗阻使肾间质体积增加了10倍以上。单侧输尿管梗阻导致同侧肾脏肾素mRNA持续增加，且胎儿肾素分布持续存在。对侧肾脏中的肾素受到抑制。梗阻肾脏中转化生长因子-β1的表达逐渐增加，但假手术肾脏在7天后下降。在出生后的头3天，正常假手术肾脏中未检测到肾EGF表达，但随着成熟其稳步增加。然而，梗阻肾脏中的EGF表达仍受到抑制。正常大鼠肾脏间质中的α-SM肌动蛋白在15日龄时消失，而在梗阻的新生肾脏中持续存在。
生长相关肽表达的变化表明，新生大鼠单侧输尿管梗阻会延迟同侧肾脏发育，这可能导致肾脏生长受损。
