Expression and regulation of bile salt export pump gene after rat hepatic warm ischemia-reperfusion

Objective To investigate the molecular mechanism of bile salt (BA) disturbance after rat hepatic warm ischemia-reperfusion.Methods Rat model with 70% hepatic warm ischemia-reperfusion was adopted.Experimental ani- mals were divided into 3 groups:group A (normal controls),group B (rats submitted to 20-rain of ischemia) and group C (rats submitted to 35-rain of ischemia).The pathologic changes of the liver were assessed by H.E.staining.The bile acid (BA) levels of bile and plasma were detected by biochemistry assay.Real-time PCR and RT-PCR were used to assess the expression of bile salt export pump (Bsep) and FXR.Simultaneously,the TNF-αlevel of liver homogenate was determined by ELISA.Results No hepatocyte necrosis was found in groups B and C.Six hours to 1d after reperfusion,the BA level of bile in group B was significantly decreased,but that in the plasma was significantly elevated.In group C,the changes of BA level both in the bile and plasma lasted for 3 days after reperfusion.Down-regulation of Bsep was concomitant with the changes of the BA level in these two groups and was inversely correlated with the TNF-αlevel.The FXR expression in group C was up-regulated for 6 h to 1 d after reperfusion.Conclusions The down-regulation of Bsep expression may lead to the disturbance of bile salt levels after reperfusion.Inflammatory cytokines might play an important role in the regula- tion of Bsep transcription after repcrfusion.