【摘要】 目的探讨鼠肝缺血再灌注后胆汁淤积发生的分子机制。方法应用70%的鼠肝缺血35 min再灌注模型,检测胆汁、血浆中胆红素、胆酸的含量；荧光定量聚合酶链反应(PCR)、免疫组织化学方法分析毛细胆管膜上胆盐输出泵(Bsep)、多耐药相关蛋白2(Mrp2)的表达；激光共聚焦方法分析Mrp2定位的改变。结果再灌注后6 h、1、3 d,Bsep的表达明显下调(mRNA表达水平分别为0．189±0．044、0．240±0．078、0．224±0．068),与胆汁、血浆中胆酸的异常改变一致。Mrp2表达的明显下调仅发生于再灌注后的6h(mRNA表达水平为0．038±0．032),与再灌注后1 h～5 d胆红素的异常变化不相符。再灌注后6h—5d,Mrp2在毛细胆管膜上定位减少、向胞浆内分布。结论Bsep表达的减少以及Mrp2定位的异常是鼠肝缺血再灌注后胆汁淤积发生的主要分子机制。更多还原

【Abstract】 Objective To investigate the mechanism of cholestasis after rat hepatic ischemia- reperfusion.Methods A model of rat 70% hepatic ischemia-reperfusion was adopted.Routine biochem- istry method detected bilirubin,bile acid levels of plasm and bile.Real time fluorescence PCR and im- munohistochemistry methods analysised expression of Bsep and Mrp2.Laser confocal methods analysised the localization of Mrp2.Results At 6h,1d,3d after reperfusion,the regulation of Bsep was significant decrease (mRNA levels:0.189±0.044,0.240±0.078,0.224±0.068 respectively) and coincidence with abnormality of bile acid leveles.Mrp2 expression was only significantly reduced at 6h (mRNA lev- els:0.038±0.032),but bilirubin levels of plasm and bile were abnormal at 1 h-5 d after reperfusion.The localization of Mrp2 continuously altered at 6 h-5 d.Conclusion Down-regulation of Bsep and abnormal localization of Mrp2 were main mechanisms of cholestasis after rat hepatic ischemia-reperfusion.更多还原