Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction
Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction
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DOI：
10.1046/j.1523-1755.1999.00612.x
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发表时间：
1999-09-01
影响因子：
19.6
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Kawada, N;Moriyama, T;Hori, M
背景。单侧输尿管梗阻（UUO）是肾脏损伤导致间质纤维化的一种成熟的实验模型。UUO肾间质纤维化的分子和细胞机制正开始被阐明。氧化应激与各种形式的肾损伤的发病机制有关；然而，其与输尿管梗阻的关系尚不清楚。为了探讨氧化应激在梗阻性肾病中的作用，我们研究了输尿管梗阻后肾脏内ne -羧甲基赖氨酸（CML）的发生和分布。CML是糖氧化引起的累积蛋白损伤的综合生物标志物。血红素氧合酶-1 (HO-1) mRNA和蛋白的表达是氧化应激的敏感和可靠的指标。输尿管梗阻发生10天后，UUO肾间质出现CML免疫反应。HO-1 mRNA在输尿管梗阻后12小时上调。输尿管梗阻后2天观察肾小球周围和小管周围间质HO-1免疫反应。这些结果强烈提示UUO肾脏间质氧化应激增加。氧化应激和间质中各种生物活性氧化产物的形成在UUO肾中起重要作用。
Background. Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to interstitial fibrosis. The molecular and cellular mechanism(s) of interstitial fibrosis in UUO kidney is beginning to be elucidated. Oxidative stress has been implicated in the pathogenesis of various forms of renal injury; however, little is known about its involvement in the setting of ureteral obstruction.Methods. To investigate the possible involvement of oxidative stress in the obstructive nephropathy, we studied the occurrence and distribution of NE-carboxymethyl-lysine (CML) in the kidneys after ureteral obstruction. CML is an integrative biomarker of the cumulative protein damage induced by glycoxidation. Heme oxygenase-l (HO-1) mRNA and protein expression, which is a sensitive and reliable indicator of oxidative stress, were also examined.Results. CML immunoreactivity was found in the interstitium of UUO kidneys 10 days after the onset ureteral obstruction. HO-1 mRNA was up-regulated as early as 12 hours after ureteral obstruction. HO-1 immunoreactivity was observed in the periglomerular and peritubular interstitium two days after ureteral obstruction.Conclusions. These results strongly suggested the presence of increased oxidative stress in the interstitium of UUO kidneys. The oxidative stress and the formation of various kind of biological active oxidative products in the interstitium are supposed to play significant roles in UUO kidney.