Effects of pretreatment with different doses of phosphocreatine on hepatic ischemia-reperfusion injury in rats

Objective To evaluate the effects of pretreatment with different doses of phosphocreatine on hepatic ischemia-repeffusion (I/R) injury in rats.Methods.Thirty male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 5 groups (n =6 each):sham operation group (group S),hepatic I/R group (group I/R),and pretreatment with different doses of phosphocreatine groups (groups P1-3).Hepatic I/R was induced by 90 min occlusion of the hepatic artery and portal vein entering the middle and left lobes of the liver followed by 4 h reperfusion in anesthetized rats.Phosphocreatine 50,150 and 450 mg/kg were injected via the tail vein at 60 min before ischemia in groups P1-3,respectively.In groups S and I/R,the equal volume of normal saline was given instead.Blood samples were taken from the abdominal aorta at 4 h of reperfusion for determination of plasma alanine aminotransferase (ALT),aspartate aminotransferase (AST),TNF-α and IL-1β concentrations.The rats were then sacrificed and the livers were removed for determination of myeloperoxidase (MPO) activity (by ELISA),intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),and cell apoptosis (by TUNEL) and for microscopic examination (by electron microscopy).Results The MPO activity in liver tissues,plasma ALT and AST activities,TNF-α and IL-1β concentrations and the number of apoptotic cells were significantly higher in groups I/R and P1-3 than in group S,while lower in groups P1-3 than in group I/R (P ＜ 0.05).The parameters mentioned above were decreasedin turn in groups P1-3 (P ＜ 0.05).Conclusion Phosphocreatine pretreatment can attenuate the hepatic I/R injury in rats in a dose-dependent manner and inhibition of the inflammatory responses is involved in the mechanism. Key words: Phosphocreatine;  Reperfusion injury;  Liver ;  Pretreatment