Renal structural and functional repair in a mouse model of reversal of ureteral obstruction
Renal structural and functional repair in a mouse model of reversal of ureteral obstruction
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DOI：
10.1681/asn.2004090771
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发表时间：
2005-12-01
影响因子：
13.6
通讯作者：
Ricardo, SD
中科院分区：
文献类型：
--
作者：
Cochrane, AL;Kett, MM;Ricardo, SD
免疫性和非免疫性肾损伤的终点通常涉及肾小球和肾小管间质纤维化。虽然许多研究都集中在导致肾纤维化的事件上，但对促进细胞修复和组织重塑的机制知之甚少。描述了一种雄性C57b1/6J小鼠单侧输尿管梗阻(UUO)逆转后肾脏损伤和修复的模型。雄性小鼠(20~25g)经10d的UUO加或不加1、2、4或6wk的UUO逆转(R-UUO)。UUO导致皮质小管细胞萎缩和肾小管扩张，外髓几乎完全消融。这与间质巨噬细胞浸润、羟脯氨酸含量增加以及I型、III型、IV型和V型胶原表达上调有关。测量呈刷状边缘的肾小管体密度作为评价R-UUO术后修复程度的指标。术后6wk，修复肾小管面积(83.7±-5.9%)较10d(32.6+/-7.3%)明显增加。与UUO小鼠的梗阻肾脏相比，这与巨噬细胞数量减少、羟脯氨酸含量减少、胶原堆积和间质基质扩张减少不谋而合。术后6周R-UUO肾GFR恢复至对侧通畅肾GFR的43%~88%。本研究描述了在UUO相关的成年小鼠肾间质基质扩张和骨髓消融后肾脏的再生潜力。
The end point of immune and nonimmune renal injury typically involves glomerular and tubulointerstitial fibrosis. Although numerous studies have focused on the events that lead to renal fibrosis, less is known about the mechanisms that promote cellular repair and tissue remodeling. Described is a model of renal injury and repair after the reversal of unilateral ureteral obstruction (UUO) in male C57b1/6J mice. Male mice (20 to 25 g) underwent 10 d of UUO with or without 1, 2, 4, or 6 wk of reversal of UUO (R-UUO). UUO resulted in cortical tubular cell atrophy and tubular dilation in conjunction with an almost complete ablation of the outer medulla. This was associated with interstitial macrophage infiltration; increased hydroxyproline content; and upregulated type I, III, IV, and V collagen expression. The volume density of kidney occupied by renal tubules that exhibited a brush border was measured as an assessment of the degree of repair after R-UUO. After 6 wk of R-UUO, there was an increase in the area of kidney occupied by repaired tubules (83.7 +/- 5.9%), compared with 10 d UUO kidneys (32.6 +/- 7.3%). This coincided with reduced macrophage numbers, decreased hydroxyproline content, and reduced collagen accumulation and interstitial matrix expansion, compared with obstructed kidneys from UUO mice. GFR in the 6-wk R-UUO kidneys was restored to 43 to 88% of the GFR in the contralateral unobstructed kidneys. This study describes the regenerative potential of the kidney after the established interstitial matrix expansion and medullary ablation associated with UUO in the adult mouse.