Involvement of NOX in the Regulation of Renal Tubular Expression of Na/K-ATPase in Acute Unilateral Ureteral Obstruction Rats
Involvement of NOX in the Regulation of Renal Tubular Expression of Na/K-ATPase in Acute Unilateral Ureteral Obstruction Rats
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DOI：
10.1159/000381858
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发表时间：
2015-01-01
期刊：
影响因子：
2.5
通讯作者：
Wang, Yu
中科院分区：
文献类型：
--
作者：
Liu, Changxuan;Song, Yi;Wang, Yu
背景/目的：据报道，在单侧输尿管梗阻(UUO)后，肾小管上皮细胞Na/K-ATPase的表达迅速减少，导致钠调节受损。本研究利用载脂蛋白验证肾组织烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶(NOX)系统参与UUO早期Na/K-ATPase表达调控的假设。方法：Wistar大鼠80只，分别行UUO或假手术，每组各50只，术后灌胃给予载脂蛋白100 mg/kg。分别于术后第1天和第3天采集肾组织标本，用免疫荧光和免疫组织化学方法检测肾组织中NOX2、NOX4和Na/K-ATPase的分布。免疫印迹法检测肾组织匀浆中HO-1、NOX2、NOX4、骨桥蛋白、Na/K-ATPase和水通道蛋白-1(AQP-1)含量，生化分析法检测丙二醛(MDA)、一氧化氮(NO)含量。用酶法检测诱导型一氧化氮合酶(INOS)和抗氧化酶的活性。结果：梗阻大鼠肾脏Na/K-ATPase、AQP-1含量降低，MDA、NOX4、NOX2、HO-1含量升高。Apoynin可减轻UUO大鼠的上述变化，并部分但显著地逆转UUO大鼠Na/K-ATPase和AQP-1的下调。然而，apocynin并不改变iNOS活性和NO的产生、骨桥蛋白的表达或抗氧化酶的活性。结论：早期UUO患者肾小管Na/K-ATPase表达下调可能与NOX系统的激活和ROS的产生有关。(C)2015年S.Karger AG，巴塞尔
Background/Aims:Renal tubular expression of Na/K-ATPase has been reported to be rapidly reduced in kidneys after unilateral ureteral obstruction (UUO), contributing to compromised sodium regulation. In this study, apocynin was utilized to test the hypothesis that the renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) system is involved in the regulation of Na/K-ATPase expression in early UUO. Methods: Eighty Wistar rats underwent UUO or sham surgery, and half of each group was administered 100 mg/kg apocynin by oral gavage after surgery. Renal tissue samples were collected on day 1 and day 3 after surgery and the distribution of NOX2, NOX4 and Na/K-ATPase was assessed by immunofluorescence and immunohistochemical staining. The Heme oxygenase-1 (HO-1), NOX2, NOX4, osteopontin, Na/K-ATPase and aquaporin-1 (AQP-1) content of renal homogenates was assessed by immunoblotting, and malondialdehyde (MDA), nitric oxide (NO) content was assessed by biochemical analyses. Activity of inducible NO synthase (iNOS) and antioxidant enzymes was assessed by enzymatic assay. Results: Kidney Na/K-ATPase and AQP-1 content was decreased, and MDA and NOX4, NOX2 and HO-1 content were increased in the obstructed kidneys of UUO rats. Apocynin attenuated these changes and partially, but significantly, reversed the downregulation of Na/K-ATPase and AQP-1 in UUO rats. However, apocynin did not alter iNOS activity and NO production, osteopontin expression or the activity of antioxidant enzymes. Conclusion: Activation of the NOX system and subsequent production of ROS are likely responsible for the downregulation of renal tubular Na/K-ATPase expression in early UUO. (C) 2015 S. Karger AG, Basel