Indomethacin Corrects Alterations Associated with Ischemia/Reperfusion in an in vitro Proximal Tubular Model
Indomethacin Corrects Alterations Associated with Ischemia/Reperfusion in an in vitro Proximal Tubular Model
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DOI：
10.1159/000313452
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Gekle, M.
中科院分区：
文献类型：
--
作者：
Sauvant, C.;Schneider, R.;Gekle, M.
背景/目标：最近的体内数据表明，吲哚美辛通过改善肾细胞存活和功能来改善缺血后的肾结果。为了研究吲哚美辛对离体近端肾小管细胞的直接影响，我们研究了吲哚美辛对缺血/再灌注（I/R）损伤标志物的影响，在体外建立的缺血和再灌注模型。方法：缺血2h，再灌注48h。在再灌注开始时加入吲哚美辛。在再灌注6、24或48 h后研究参数。结果如下：吲哚美辛通过坏死和凋亡、释放前列腺素E2、诱导I/R诱导蛋白、去分化或诱导诱导型一氧化氮合酶而减少细胞死亡。此外，吲哚美辛完全防止缺血引起的基底外侧有机阴离子转运的抑制。吲哚美辛不影响缺血介导的核因子-κ B或单核细胞趋化蛋白1的诱导。缺血不诱导基质蛋白合成。结论：我们已经证明：（a）局部缺血后应用的吲哚美辛对模型局部缺血后的近端小管细胞存活具有有益作用，并通过直接作用于近端小管细胞而损害由局部缺血特征性诱导的参数变化;（B）近端小管细胞的炎症反应不受吲哚美辛的影响，和（c）在分离的近端小管细胞中，模型局部缺血后不发生纤维化。版权所有（C）2010 S. Karger AG，巴塞尔
Background/Aims: Recent in vivo data indicate that indomethacin improves renal outcome after ischemia via improvement of renal cell survival and function. To examine direct effects of indomethacin on isolated proximal tubular cells, we investigated the influence of indomethacin on markers of ischemia/reperfusion (I/R) damage in an established in vitro model of ischemia and reperfusion. Methods: Ischemia was applied for 2 h followed by reperfusion for up to 48 h. Indomethacin was added at the beginning of reperfusion. Parameters were investigated after 6, 24 or 48 h of reperfusion. Results: Indomethacin diminished cell death by necrosis and apoptosis, release of prostaglandin E 2, induction of I/R-induced protein, dedifferentiation or induction of inducible nitric oxide synthase. Moreover, indomethacin totally prevented the ischemia-induced inhibition of basolateral organic anion transport. Indomethacin did not affect ischemia-mediated induction of nuclear factor-kappa B or monocyte chemoattractant protein 1. Ischemia did not induce matrix protein synthesis. Conclusions: We have shown that: (a) indomethacin applied after ischemia has a beneficial effect on proximal tubule cell survival after model ischemia and impairs changes of parameters characteristically induced by ischemia via direct action on proximal tubule cells; (b) the inflammatory response of proximal tubule cells was not affected by indomethacin, and (c) fibrosis does not take place after model ischemia in isolated proximal tubule cells. Copyright (C) 2010 S. Karger AG, Basel