大鼠肝缺血再灌注后高胆红素血症与Mrp2、Mrp3表达及定位改变的关系

目的 研究大鼠肝脏缺血再灌注后多耐药相关蛋白2(Mrp2)、多耐药相关蛋白3(Mrp3)表达及定位的改变,探讨肝缺血再灌注后发生高胆红素血症的分子机制.方法 实验分为假手术组(Sham组)和肝缺血30 min再灌注组(IR组).检测血浆和胆汁中DBIL含量.RT-PCR和免疫组织化学方法检测毛细胆管膜上Mrp2和基底膜...

RELATIONSHIP BETWEEN THE EXPRESSION AND LOCALIZATION CHANGES OF MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2,MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 3 AND HYPERBILIRUBINEMIA AFTER HEPATIC ISCHEMIA-REPERFUSION IN RATS

Objective To study the expression and localization of multi-drug resistance-associated protein 2(Mrp2),multi-drug resistance-associated protein 3(Mrp3) changes and investigate the molecular mechanism of hyperbilirubinemia after hepatic ischemia-reperfusion in rats.Methods Rats were divided into a sham operation group(Sham group) and a 30 min ischemia-reperfusion group(IR group).The levels of plasma DBIL and bile DBIL were detected.RT-PCR and Immunohistochemistry methods were used to detect the expression and localization of Mrp2 in the canalicular membrane and Mrp3 in the basolateral membrane.Results Compared with Sham group,the levels of plasma DBIL were significantly increased and the bile DBIL levels were significantly reduced 1 h~1 d after reperfusion in IR group(P<0.05).The expression of Mrp2 mRNA was significantly reduced 1 h~6 h after reperfusion in IR group than in Sham group(P<0.05);No localization of Mrp2 protein in the canalicular membrane was found but it appeared in "vesicles" under the canalicular membrane 1 d after reperfusion.The expression of Mrp3 mRNA was significantly reduced 1 h~1 d after reperfusion in IR group than in Sham group(P<0.05);At 1 h~1 d after reperfusion,the staining intensity of Mrp3 protein was significantly increased in the basement membrane.Conclusion Down-regulation and abnormal localization of Mrp2 as well as up-regulation of Mrp3 were molecular mechanisms of hyperbilirubinemia after hepatic ischemia-reperfusion in rats.