Upregulation of rat renal cortical organic anion transporter (OAT1 and OAT3) expression in response to ischemia/reperfusion injury
Upregulation of rat renal cortical organic anion transporter (OAT1 and OAT3) expression in response to ischemia/reperfusion injury
复制标题
缺血/再灌注损伤时大鼠肾皮质有机阴离子转运蛋白（OAT1 和 OAT3）表达的上调
DOI：
10.1159/000129073
复制
发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Yu, Xue-Qing
中科院分区：
文献类型：
--
作者：
Zhang, Rui;Yang, Xiao;Yu, Xue-Qing
背景/目标：位于基底外侧膜的肾有机阴离子转运蛋白（OAT 1和OAT 3）介导有机阴离子从血液摄取到近端小管。本研究旨在研究肾缺血/再灌注损伤（IRI）对肾皮质OAT 1和OAT 3表达的影响及其功能影响。研究方法：雄性大鼠行右肾切除、左肾蒂夹闭50 min或假手术，再灌注1、2、4、6 d。采用RT-PCR、免疫组化和Western blot检测OAT 1和OAT 3的表达。Na+-K+-ATP酶活性也进行了测定。结果如下：与假手术大鼠相比，IRI大鼠第1天对氨基马尿酸的肾脏清除率显著降低，并在肾小管损伤恢复后恢复正常。IRI后第1天，肾皮质匀浆和基底外侧膜中OAT 1和OAT 3的mRNA和蛋白水平显著升高，第2、4天，肾组织中OAT 1和OAT 3的表达逐渐降低，但仍显著高于假手术组。肾皮质Na+-K+-ATP酶活性在缺血再灌注后第1天明显下降，第2、4、6天逐渐升高。结论：肾对氨基马尿酸清除率在IRI时降低，但在IRI早期肾皮质OAT 1和OAT 3表达显著升高，可能对某些药物和毒性化合物的肾排泄产生实质性影响。版权所有（C）2008 S. Karger AG，巴塞尔。
Background/Aims: Renal organic anion transporters (OAT1 and OAT3) localized in the basolateral membrane mediate the uptake of organic anions from the blood into proximal tubules. This study aimed to examine the effects of renal ischemia/reperfusion injury (IRI) on the expression of cortical renal OAT1 and OAT3 and the functional impact. Methods: Male rats underwent a right nephrectomy and clamping of the left renal pedicle for 50 min or sham operation, followed by reperfusion for 1, 2, 4 and 6 days. The expression of OAT1 and OAT3 was detected by RT-PCR, immunohistochemistry and Western blot analysis. Na+-K+-ATPase activity was also estimated. Results: The renal clearance of para-aminohippurate was significantly decreased on day 1 in IRI rats compared with sham-operated rats and returned to normal when the tubular injury recovered. There were significant increases in the mRNA and protein levels of OAT1 and OAT3 in renal cortex homogenates and basolateral membranes on day 1 after IRI, while on days 2 and 4 after IRI, the renal expression of OAT1 and OAT3 decreased gradually but was still significantly higher than that of the sham-operated rats. The Na+-K+-ATPase activity in renal cortex homogenates decreased significantly on day 1 after IRI but gradually increased on days 2, 4 and 6. Conclusions: Renal para-aminohippurate clearance was depressed in response to IRI; however, the expressions of renal cortex OAT1 and OAT3 were significantly elevated in the early stage of IRI which may have substantial impact on renal excretion of some drugs and toxic compounds. Copyright (C) 2008 S. Karger AG, Basel.