Remifentanil Preconditioning Protects Against Hepatic Ischemia Reperfusion Injury In The Cirrhotic Rats

Objective: To explore the protective effect of remifentanil on apoptosis in cirrhotic rats subjected to ischemia reperfusion injury.Method: Sixty-one male SD rats weighting 170 g ± 10 g received 40%CCl4intragastrically during 8 weeks.All animals received standard rat chow ad libitum,but the 10% alcohol instead of the water for 6 weeks.The cirrhotic rats were randomly divided into six groups.Sham operation group(group S,n=7): dissecting the branches of hepatic artery,portal vein in the median and left lateral hepatic lobes but not clamping;Ischemia/reperfusion group(group IR,n=7): clamping the branches for 30 min,followed by a 1.5-hour period of reperfusion.Normal saline group(group NS,n=7): 0.9% saline was infused for 15 min and stopped 10 min before occlusion procedure.The transfusion volume is the same to the group RPC.Remifentanil preconditioning group(group RPC,n =21): Remifentanil preconditioning group was divided into 3 subgroups of 7 rats each: a 15-min infusion of 0.4,2 and10?g·kg-1·min-1(group R1,R2 and R3,respectively),finishing 10 min before the IR procedure.After reperfusion,blood was collected to separate the serum for analysis of ALT,AST.The median hepatic tissue was collected for homogenate to detect SOD,MDA and western blot analysis of Cleaved-Caspase-3.The left hepatic tissue fixed in10% formalin and embedded in paraffin for histopathology examination by HE staining,the immunohistology of Caspase-3 and apoptotic cell detection by TUNEL.Result: The liver histology of all groups exhibited different sizes pseudolobule.There were serious inflammatory cells infiltrating and congesting around the portal area and sinusoidal obviously in group IR but slight in group R2,R3.And these changes in group S were less than other five groups.In comparison with group S,the level of serum transaminase and hepatic MDA were increased,the activities of SOD,Caspase-3 and apoptotic index were elevated among other groups(P<0.01).Compared with group IR,remifentanil pretreatment(infusion of 2 and 10?g/kg/min)decreased concentrations of serum ALT,AST and hepatic MDA,reduced the activity of and the amount of apoptotic hepatocyte increased the concentrations of hepatic SOD(P<0.01).But the changes weren't observed in group R1(administration0.4?g/kg/min remifentanil)((P>0.05)Conclusion: Remifentanil preconditioning could protect the cirrhotic rats against hepatic ischemia/reperfusion injury by inhibiting the oxidative stress and decreasing the apoptosis.This effect in the R2 and R3 group(infusion of 2 and 10?g/kg/min,respectively)can be observed,but not in R1 group(infusion of 0.4?g/kg/min).