Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats
Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats
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DOI：
10.1152/ajprenal.00441.2003
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发表时间：
2004-12-01
影响因子：
4.2
通讯作者：
Felsen, D
中科院分区：
文献类型：
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作者：
Ito, K;Chen, J;Felsen, D
单侧输尿管梗阻（UUO）解除后肾脏损害的进展已被证实，特别是在新生大鼠中。我们对5组成年大鼠在UUO缓解3天后的肾功能和肾损害进行评估：1组，未给药；第2组，3天UUO；3 ~ 5组、3 d不动后缓解；第三组，缓解7天；第4组，缓解14天；第5组，28天缓解。评估肾小球滤过率（GFR）、肾血流量（RBF）、组织转化生长因子- β (tgf - β)、间质纤维化和成纤维细胞表达、小管凋亡、巨噬细胞浸润、一氧化氮合酶（NOS）表达、尿硝酸盐/亚硝酸盐(NO（2)/NO(3)）。UUO治疗3天后，RBF和GFR降至基线的10%以下。先前梗阻肾（POK）的GFR和RBF在缓解后14天恢复到基线水平。3 ~ 5组POK组织tgf - β(1)和间质纤维化均明显高于1、2组。5组POK中浸润性巨噬细胞、成纤维细胞、凋亡小管细胞数量均高于1组。尿NO(2)/NO(3)在UUO缓解后3 ~ 27天显著高于基线。小管中NOS异构体表达增加。由于间质纤维化导致肾功能下降，这些结果表明，从长期来看，功能的急性恢复可能会被发现的进行性肾纤维化所损害。此外，在UUO缓解时进行药物干预，针对纤维化过程，可能有助于肾功能的长期恢复。
Progression of renal damage after relief of unilateral ureteral obstruction (UUO) has been demonstrated, especially in neonatal rats. We evaluated renal function and renal damage after relief of 3-day UUO in five groups of adult rats: group 1, no treatment; group 2, 3-day UUO; groups 3-5, 3-day UUO followed by relief; group 3, 7-day relief; group 4, 14-day relief; and group 5, 28-day relief. Glomerular filtration rate (GFR), renal blood flow (RBF), tissue transforming growth factor-beta (TGF-beta), interstitial fibrosis and fibroblast expression, tubular apoptosis, macrophage infiltration, expression of nitric oxide synthases ( NOS), and urinary nitrate/nitrite (NO(2)/NO(3)) were evaluated. RBF and GFR were decreased to < 10% of baseline by 3 days of UUO. GFR and RBF in a previously obstructed kidney (POK) returned to baseline by 14 days after relief. Both tissue TGF-beta(1) and interstitial fibrosis were significantly higher in POK of groups 3-5 compared with groups 1 and 2. In group 5, the numbers of infiltrating macrophages, fibroblasts, and apoptotic tubular cells were higher in POK compared with group 1. Urinary NO(2)/NO(3) was significantly higher than baseline from 3 to 27 days after relief of UUO. Expression of NOS isoforms was increased in tubules. As interstitial fibrosis contributes to decreased renal function, these results suggest that the acute recovery in function may be compromised in the long term by the progressive renal fibrosis which was found. Furthermore, pharmacological intervention at the time of relief of UUO, targeted to fibrotic processes, may contribute to long-term recovery of renal function.