Protective effects of estrogen on hepatic ischemia-reperfusion injury related to nuclear factor-κB/IκB pathway in rat model

Objective To study the effects of estrogen (E2) on nuclear factor-κB (NF-κB)/IκB pathway in rat model of hepatic ischemia-reperfusion (I/R) injury.Methods Models of rats with hepatic I/R were established.Male SD rats were randomly divided into three groups:Sham group,I/R group and I/R + E2 group.After 1,3 and 6 h of reperfusion,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum were determined.The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the hepatic tissue were detected.Histologic changes of the liver were observed.The expression of NF-κB was detected by immunohistochemistry,and the activity of IκB-α and ICAM-1 was measured by Western blotting.Cell apoptosis was measured by flow cytometry.Results The levels of ALT and AST in I/R group were significantly higher than those in I/R + E2 group after reperfusion and reached peak at 6 h ( P ＜ 0.05 ).As compared with that in I/R + E2 group and Sham group,the apoptosis index of the hepatocytes was significantly increased in I/R group (P ＜0.01 ).In I/R group the level of IκB-α protein expression was decreased,while the expression of NF-κB was increased (P ＜ 0.05 ),which was similar with the changes in MDA and ICAM-1.The change of SOD was contrary to that of MDA and ICAM-1.The obvious I/R injury was observed under a light microscope in I/R group,including congestion in liver sinusoids,hepatocyte swelling,inflammatory cell infiltration and necrosis of hepatocytes in some areas of the livers.In Sham group and I/R + E2 group,hepatic tissue injury was significantly improved.Conclusion E2 significantly protects the liver from hepatic I/R injury probably by interfering with NF-κB/IκB pathway,inhibiting lipid peroxidation,and reducing the release of inflammatory mediators and the apoptosis. Key words: Liver; Ischemia; Reperfusion injury; Estrogen; ICAM-1