Ischemia-reperfusion of rat livers decreases liver and increases kidney multidrug resistance associated protein 2 (Mrp2).
Ischemia-reperfusion of rat livers decreases liver and increases kidney multidrug resistance associated protein 2 (Mrp2).
复制标题
大鼠肝脏缺血再灌注会导致肝脏多药耐药相关蛋白 2 (Mrp2) 减少，肾脏多药耐药相关蛋白 2 (Mrp2) 增加。
DOI：
10.1093/toxsci/kfm261
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Klaassen,CurtisD
中科院分区：
文献类型：
--
作者：
Tanaka,Yuji;Chen,Chuan;Maher,JonathanM;Klaassen,CurtisD
肝移植过程中肝缺血再灌注损伤可导致胆汁淤积和远端脏器功能障碍。多药耐药相关蛋白（Mrps）是已知的外排转运体，可转运多种底物，如两性化学物质、有机阴离子和内源性分子。本研究旨在探讨肝脏IR损伤对大鼠肝脏和肾脏Mrps表达的影响。雄性Sprague-Dawley大鼠局部肝缺血60 min。在再灌注后的不同时间（0、3、6、24和48小时），摘取缺血叶和肾脏。采用支链DNA法、Western blot法和组织免疫荧光法检测肝脏和肾脏中Mrps的RNA和蛋白表达。IR后肝脏中Mrp2 mRNA和蛋白表达降低。相反，IR后肾脏中Mrp2 mRNA和蛋白的表达增加。肾组织Mrp3 mRNA和Mrp4 mRNA及蛋白表达在IR后短暂升高。Mrp2免疫荧光染色的强度与IR后肝脏和肾脏中Mrp2表达的变化相对应，Western blot分析发现Mrp2定位于两组织的顶膜结构域。这些结果表明，肝脏IR后，肝脏Mrp2下调，肾脏Mrp2上调。肝脏Mrp2的减少可能导致胆汁淤积，而肾脏Mrp2的增加可能保护肝脏IR后免受氧化应激和/或炎症。
Hepatic ischemia-reperfusion (IR) injury during liver transplantation can lead to cholestasis and remote organ dysfunction. Multidrug resistance–associated proteins (Mrps) are efflux transporters known to transport a diverse set of substrates, such as amphipathic chemicals, organic anions, and endogenous molecules. The purpose of this study was to determine the effect of hepatic IR injury on the expression of Mrps in rat liver and kidney. Male Sprague-Dawley rats were subjected to 60 min of partial hepatic ischemia. At various times after reperfusion (0, 3, 6, 24, and 48 h), the ischemic lobes were harvested as well as kidneys. RNA and protein expression of Mrps in livers and kidneys were determined by the branched DNA method, Western blot analysis, and tissue immunofluorescence. Mrp2 mRNA and protein expression in livers decreased after IR. Conversely, Mrp2 mRNA and protein expression in kidneys increased after IR. Mrp3 mRNA expression, and Mrp4 mRNA and protein expression in kidneys transiently increased after IR. The intensity of immunofluorescent staining of Mrp2 corresponded to changes in Mrp2 expression in livers and kidneys after IR as detected by Western blot analysis and was localized to the apical membrane domain in both tissues. These results demonstrate that after hepatic IR, downregulation of hepatic Mrp2 and upregulation of renal Mrp2 occur. These decreases in hepatic Mrp2 may contribute to cholestasis, yet increases in kidney may protect from oxidative stress and/or inflammation after hepatic IR.