Low-dose indomethacin after ischemic acute kidney injury prevents downregulation of Oat1/3 and improves renal outcome.
Low-dose indomethacin after ischemic acute kidney injury prevents downregulation of Oat1/3 and improves renal outcome.
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缺血性急性肾损伤后小剂量吲哚美辛可防止 Oat1/3 下调并改善肾脏预后
DOI：
10.1152/ajprenal.00268.2009
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Sauvant C
中科院分区：
文献类型：
--
作者：
Schneider R;Meusel M;Renker S;Bauer C;Holzinger H;Roeder M;Wanner C;Gekle M;Sauvant C
我们以前已经表明，表达的肾脏有机阴离子转运蛋白Oat 1和Oat 3减少前列腺素E2（PGE 2）和这两个转运蛋白下调后，肾缺血。由于PGE 2在肾缺血后增加，并由环氧化酶（考克斯）产生，我们研究了考克斯抑制剂吲哚美辛对缺血性急性肾损伤（iAKI）后Oat 1/3表达的影响。通过双侧肾动脉夹闭45分钟在大鼠中诱导iAKI。一旦再灌注开始，立即腹腔内给予吲哚美辛（1 mg/kg）。假手术处理的动物作为对照。通过qPCR和Western印迹测定Oat 1/3。采用酶联免疫吸附法测定血、尿PGE 2。测定单核细胞/巨噬细胞的侵袭。测定肾小球滤过率和肾血浆流量。缺血24 h后检测各项指标。计算PAH净分泌量、PGE 2清除率和PGE 2分泌量。在钳夹动物中，吲哚美辛恢复了Oat 1/3的表达，以及PAH净分泌、PGE 2清除或PGE 2分泌。此外，通过肾小球滤过和PAH清除率测定，吲哚美辛显著改善了肾功能。吲哚美辛不影响缺血诱导的单核/巨噬细胞的侵袭。总之，我们的研究表明，缺血后应用低剂量吲哚美辛可防止再灌注期间缺血诱导的Oat 1/3下调，并对iAKI后的肾功能具有实质性保护作用。低剂量吲哚美辛对肾脏结局的有益作用可能是由于与抑制炎症不同的作用。根据PAH净分泌减少，缺血和再灌注后内源性有机阴离子（PGE 2）的肾脏排泄也受损。
We have previously shown that expression of renal organic anion transporters Oat1 and Oat3 is diminished by prostaglandin E2(PGE2) and that both transporters are downregulated after renal ischemia. Because PGE2is increased after renal ischemia and is generated by cyclooxygenases (COX), we investigated the effect of the COX inhibitor indomethacin on expression of Oat1/3 after ischemic acute kidney injury (iAKI). iAKI was induced in rats by bilateral clamping of renal arteries for 45 min. Indomethacin (1 mg/kg) was given intraperitoneally as soon as reperfusion started. Sham-treated animals served as controls. Oat1/3 were determined by qPCR and Western blot. PGE2in blood and urine was measured by enzyme-linked immunosorbent assay. Invasion of monocytes/macrophages was determined. Glomerular filtration rate and renal plasma flow were determined. All parameters were detected 24 h after ischemia. PAH net secretion, as well as clearance and secretion of PGE2were calculated. In clamped animals, indomethacin restored expression of Oat1/3, as well as PAH net secretion, PGE2clearance, or PGE2secretion. Additionally, indomethacin substantially improved kidney function as measured by glomerular filtration and PAH clearance. Indomethacin did not affect ischemia-induced invasion of monocytes/macrophages. In conclusion, our study indicates that low-dose indomethacin applied after ischemia prevents ischemia-induced downregulation of Oat1/3 during reperfusion and has a substantial protective effect on kidney function after iAKI. The beneficial effect of low-dose indomethacin on renal outcome is likely due to an effect different from inhibition of inflammation. In accordance to the decreased PAH net secretion, renal excretion of an endogenous organic anion (PGE2) is also impaired after ischemia and reperfusion.
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一氧化氮和前列腺素 E2 在急性肾低灌注中的作用
影响因子：
2.5
作者：
H. Tokuyama;K. Hayashi;H. Matsuda;E. Kubota;M. Honda;K. Okubo;I. Takamatsu;Y. Ozawa;T. Saruta
通讯作者：
T. Saruta
一氧化氮和前列腺素在慢性肾缺血中的狭窄依赖性作用。
DOI：
--
发表时间：
2002
期刊：
AJP - Renal Physiology
影响因子：
--
作者：
H. Tokuyama;K. Hayashi;H. Matsuda;E. Kubota;M. Honda;K. Okubo;Y. Ozawa;T. Saruta
通讯作者：
T. Saruta
影响因子：
19.6
作者：
Bonventre, JV;Zuk, A
通讯作者：
Zuk, A
DOI：
10.1152/ajprenal.00405.2002
发表时间：
2003-04-01
影响因子：
4.2
作者：
Sweet, DH;Chan, LMS;Pritchard, JB
通讯作者：
Pritchard, JB
影响因子：
19.6
作者：
Matsuzaki, T.;Watanabe, H.;Saito, H.
通讯作者：
Saito, H.