Effect of propofol pretreatment against hepatic ischemia-reperfusion injury on mitochondrial permeability transition pore in rats / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the protective effect of propotol against hepatic ischemiareperfusion injury in rats on mitochondrial permeability transition pore (MPTP) and the mechanism of GSK-3β.Methods Thirty SD rats were randomly assigned into five groups (n =6):sham operation group (S group),ischemia reperfusion group (I/R group),CsA pretreatment group (C group),propofol pretreatment group (P group),and propofol plus atractyloside pretreatment group (A + P group).Nauta liver ischemia-reperfusion rat model was used.Liver lobes were subjected to warm ischemia for 60min and then reperfusion for 120 min.In P group,propofol [12 mg/(kg · h)] was administered in the femoral vein for 30 min before ischemia until the end of reperfusion.In C group,CsA (2 mg/kg) was administered in the femoral vein for 20min before ischemia.In A + P group,20 μmol/kg of atractyloside was given through the femoral vein 10min before the injection of propofol.Rats were sacrificed at the end of reperfusion,and venous blood and hepatic tissue specimens from the same part of ischemia were obtained from different groups.Results Compared with S group,the AST and ALT levels were increased significantly,mitochondrial swelling were increased and mitochondrial membrane potential were decreased significantly in I/R group and A + P group.Casepase-3 were increased significantly and p-GSK3β Ser9 were decreased significantly in I/R group and A + P group.Compared with I/R group,the content of AST and ALT were decreased significantly,mitochondrial swelling were decreased and mitochondrial membrane potential were increased significantly,casepase-3 release were decreased significantly and p-GSK3β Ser9 were increased significantly in P group and C group.GSK-3β in each group displayed no significant difference.Conclusions Propofol can significantly reduce hepatic ischemia-reperfusion injury.The protective effect of propofol may be achieved via the inhibition of GSK-3β activation,increased p-GSK-3β Ser9 level,suppressing MPTP opening and decreasing hepatocytes apoptosis.