Recovery following relief of unilateral ureteral obstruction in the neonatal rat
Recovery following relief of unilateral ureteral obstruction in the neonatal rat
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DOI：
10.1046/j.1523-1755.1999.055003793.x
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发表时间：
1999-03-01
影响因子：
19.6
通讯作者：
Wolstenholme, JT
中科院分区：
文献类型：
--
作者：
Chevalier, RL;Kim, A;Wolstenholme, JT
背景阻塞性肾病是婴儿和儿童肾功能不全的主要原因。本研究旨在区分暂时性单侧输尿管梗阻（UUO）对发育中肾脏的可逆性和不可逆性细胞后果。在出生后的48小时内对大鼠进行UUO或假手术，并在5天后将梗阻移除（或留在原位）。14或28天后取出肾脏用于研究。在另外的组中，在梗阻5天结束时切除肾脏。测定了小动脉中血管紧张素的免疫反应性分布，并测定了小管和间质中表皮生长因子、转化生长因子-β 1、簇蛋白、波形蛋白和α-平滑肌肌动蛋白的分布。通过形态计量学测定肾小球数量、肾小球成熟、肾小管萎缩和间质胶原沉积。增殖细胞核抗原法检测肾细胞增殖，TdT尿苷缺口末端标记法检测肾细胞凋亡。以菊糖清除率测定肾小球滤过率。持续性UUO时，肾微血管肾素维持胎儿分布;梗阻解除后，这种分布部分逆转。虽然肾小球成熟也延迟，肾小球体积减少UUO，梗阻的缓解阻止了肾小球体积的减少。虽然梗阻的缓解并没有逆转肾单位数量减少40%，但梗阻后肾脏的肾小球滤过率正常。梗阻的缓解并没有改善肾小管细胞增殖，仅部分减少UUO诱导的细胞凋亡。这与管状表皮生长因子的持续减少有关。此外，梗阻的缓解减少了但没有使转化生长因子β 1、簇蛋白和波形蛋白的肾小管表达正常化，所有这些都是持续性肾小管损伤的证据。梗阻的缓解显著降低了间质纤维化和间质成纤维细胞α-平滑肌肌动蛋白的表达，但未恢复至正常水平。新生大鼠梗阻的缓解可减轻但不能逆转UUO 5天引起的肾血管、肾小球、肾小管和间质损伤。梗阻后肾脏中残留肾单位的超滤和残留肾小管间质损伤可能导致日后肾功能恶化。
Background. Obstructive nephropathy is a primary cause of renal insufficiency in infants and children. This study was designed to distinguish the reversible and irreversible cellular consequences of temporary unilateral ureteral obstruction (UUO) on the developing kidney.Methods. Rats were subjected to UUO or sham operation in the first 48 hours of life, and the obstruction was removed ave days later (or was left in place). Kidneys were removed for study 14 or 28 days later. In additional groups, kidneys were removed at the end of five days of obstruction. Immunoreactive distribution of renin was determined in arterioles, and the distribution of epidermal growth factor, transforming growth factor-beta 1, clusterin, vimentin, and alpha-smooth muscle actin was determined in tubules andior interstitium. The number of glomeruli, glomerular maturation, tubular atrophy, and interstitial collagen deposition was determined by morphometry. Renal cellular proliferation and apoptosis were measured by proliferating cell nuclear antigen and the TdT uridine-nick-end-label technique, respectively. The glomerular filtration rate was measured by inulin clearance.Results. Renal microvascular renin maintained a fetal distribution with persistent UUO; this was partially reversed by the relief of obstruction. Although glomerular maturation was also delayed and glomerular volume was reduced by UUO, the relief of obstruction prevented the reduction in glomerular volume. Although relief of obstruction did not reverse a 40% reduction in the number of nephrons, the glomerular filtration rate of the postobstructed kidney was normal. The relief of obstruction did not improve tubular cell proliferation and only partially reduced apoptosis induced by UUO. This was associated with a persistent reduction in the tubular epidermal growth factor. In addition, the relief of obstruction reduced but did not normalize tubular expression of transforming growth factor-beta 1, clusterin, and vimentin, all of which are evidence of persistent tubular injury. The relief of obstruction significantly reduced interstitial fibrosis and expression of alpha-smooth muscle actin by interstitial fibroblasts, but not to normal levels.Conclusions. The relief of obstruction in the neonatal rat attenuates, but does not reverse, renal vascular, glomerular, tubular, and interstitial injury resulting from five days of UUO, Hyperfiltration by remaining nephrons and residual tubulointerstitial injury in the postobstructed kidney are likely to lead to deterioration of renal function later in life.