Effects of remifentanil preconditioning on hepatic ischemia-reperfusion injury in rats with liver cirrhosis

Objective To evaluate the effect of remifentanil preconditioning on hepatic ischemiarepeffusion (I/R) injury in rats with liver cirrhosis.Methods Healthy male Sprague-Dawley rats,weighing 160180 g,received 40％ tetrachloride carbon 3 ml/kg (in peanut oil) intragastrically twice a week for 8 weeks to induce liver cirrhosis.Thirty-five rats with liver cirrhosis were randomly divided into 5 groups (n =7 each) using a random number table:sham operation group (group S),group I/R,and preconditioning with different does of remifentanil groups (R1,R2 and R3 groups).Hepatic I/R injury was induced by clamping the branches of hepatic artery,portal vein and common bile duct in the left and median hepatic lobes for 30 min followed by 90 min reperfusion in anesthetized rats with liver cirrhosis.In R1,R2 and R3 groups,remifentanil was infused intravenously at 0.4,2.0 and 10.0 μg· kg-1· min-1 for 15 min,respectively,and the rats were exposed to ischemia for 30 min followed by 30 reperfusion starting from 10 min after infusion was stopped.At 90 min of reperfusion,blood samples were collected from the abdominal aorta for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.The rats were then sacrificed and livers were removed for determination of superoxide dismutase (SOD) activity,malondialdehyde (MDA) content,and expression of activated caspase-3 (using immunohistochemistry and Western blot analysis) and for detection of cell apoptosis in hepatic tissues.Apoptotic index was calculated.Results Compared with group S,the serum ALT and AST activities,MDA content and apoptotic index were significantly increased,SOD activity was decreased,and the expression of activated caspase-3 was up-regulated in I/R,R1,R2 and R3 groups.Compared with group I/R,no significant changes were found in the indexes mentioned above in group I/R,and the serum ALT and AST activities,MDA coment and apoptotic index were significantly decreased,SOD activity was increased,and the expression of activated caspase-3 was down-regulated in R2 and R3 groups.Conclusion Remifentanil preconditioning can reduce hepatic I/R injury in rats with liver cirrhosis,and the mechanism is related to inhibition of the lipid peroxidation and cell apoptosis. Key words: Piperidines;  Ischemic preconditioning;  Liver cirrhosis;  Reperfusion injury ;  Liver