Objective      To determine the expression of transcriptional factors liver receptor homolog 1 (NR5A2) and specificity protein 1 (SP1) in obstructive cholestasis

explore their expression levels with that of multidrug resistance-associated protein 3 (MRP3)

and investigate the role of MRP3 in li

ver injury from the accumulation of toxic bile acids under cholestatic condition.       Methods      Live tissue samples from 15 patients with identified obstructive cholestasis and 15 control patients excluded liver diseases were collected. The expression of NR5A2 and SP1 was detected with RT-PCR and immunofluorescence staining. The correlation of the expression of MRP3 mRNA with the levels of NR5A2 and SP1

and with serum levels of ALT and AST were analyzed by liner regression. The correlation of the expression level of MRP3 protein and hepatic necrosis in human cholestasis (HE staining) was also studied.       Results      The expression levels of NR5A2 and SP1 were extremely increased in human cholestatic tissues

compared with normal controls (3.7-fold

P0.01

and 3.2-flod

P0.01

respectively). NR5A2 and SP1 were predominately expressed in the nucleus of cholestatic hepatocytes but not in that of normal controls. There was a significantly positive correlation of the expression levels of NR5A2 and SP1 proteins with hepatic MRP3 mRNA level in cholestatic tissues (r

2

=0.47

P0.05

and r

2

=0.51

P0.01

respectively). HE staining also indicated that hepatic necrosis was more severe in the tissue samples with elevated expression of MRP3 protein under cholestatic condition. There was a markedly negative correlation between MRP3 protein expression and serum ALT and AST levels (r

2

=0.52

P0.01

and r

2

=0.39

P0.05).        Conclusion      Hepatic NR5A2 and SP1 are upregulated in the liver tissue under cholestatic condition

which are positively correlated with the expression of MRP3. Meanwhile

the elevated MRP3 expression may alleviate the liver injury caused by the accumulation of toxic bile acids under cholestatic condition.