Objective To investigate the expression and significance of uncoupling protein 2(UCP-2) in rats with obstructive jaundice and bile flow restoration,and to explore the molecular mechanisms of metabolic disorders and oxidative damage caused by obstructive jaundice.Methods Thirty-six healthy male Wistar rats were randomly divided into six groups:sham-operation group(group A),obstructive jaundice for one week(group B),obstructive jaundice for two weeks(group C),obstructive jaundice for one week followed by recanalization for one week(group D),obstructive jaundice for ten days followed by recanalization for one week(group E),and obstructive jaundice for two weeks followed by recanalization for one week(group F).The serum levels of alanine aminotransferase(ALT),direct bilirubin(DBil),and total bilirubin(TBil) were measured.Morphological changes in hepatic tissues were observed under a light microscope.Expression of UCP-2 mRNA in hepatic tissues was assessed by RT-PCR.Results After induction of obstructive jaundice,the serum levels of ALT,DBil,and TBil in groups B and C were significantly elevated compared with those in group A(P < 0.05),and group C had even higher serum levels compared with group B(P < 0.05).Hepatic tissues of group B and C displayed pathological changes,including swelling of hepatocytes,infiltration of inflammatory cells,and bile duct hyperplasia in the portal area.Piecemeal necrosis of liver cells was observed in group C,which was accompanied by more serious pathological changes and increased proliferation of bile ducts and fibrous tissues.Compared with group A,groups B and C showed increased expression of UCP-2 mRNA in hepatic tissues(P < 0.05),and the increase was more prominent in group C(P < 0.05).After restoration of bile flow,the serum levels of ALT,DBil,and TBil in groups D,E and F decreased to varying degrees,and liver morphology tended to be normal.Expression of UCP-2 mRNA in group D was significantly higher than that in group B(P < 0.05),but lower than that in groups E and F(P < 0.05).Group F had significantly lower expression of UCP-2 mRNA than group C(P < 0.05).No significant difference in UCP-2 expression was observed between groups E and F(P > 0.05).Conclusion Expression of UCP-2mRNA in liver is upregulated with the induction of obstructive jaundice,and the level of expression is positively correlated with the duration of obstruction.With early relief of obstruction via bile flow restoration,active regeneration of hepatic tissues occurs,leading to temporary increase in UCP-2 expression.However,with prolonged obstruction,extensive liver damage prevents active regeneration of hepatic tissues,which results in slightly decreased expression of UCP-2.These results indicate that upregulation of UCP-2 may be one of the major mechanisms of metabolic disorders after obstructive jaundice.
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