ABSTRACT
Objective To investigate the protective effects of different doses of fasudil on hepatic ischemia/reperfussion (I/R) injury in rats with liver cirrhosis.Methods Cirrhosis was induced in rats by subcutaneous injection of 60％ carbon tetrachloride (CC14) corn oil solution (0.4 ml/100 g) twice a week for twelve weeks.Five percent of alcohol was given intermittently in drinking water.Then 40 cirrhotic rats were randomized into 4 groups.In sham group,sham operation was performed.In I/R group A and B,whole rat livers were subjected to warm ischemia by clamping the hepatic artery and portal vein for 30 min.In group A,the selected rats were pretreated with low-dose fasudil 1 mg/kg (intraperitoneal injection) 30 min before the induction of ischemia,and in group B,with high-dose 10 mg/kg.The serum levels of alanine aminotransferase (ALT) and endothelin-1 (ET-1),and the liver tissue superoxide dismutase (SOD)activity,malondialdehyde (MDA) content,the expression of HIF-1a (hypoxia-inducible fador-1a) were measured after reperfusion for 6 hours.Hepatic pathologic changes were observed under microscope.Results Compared with I/R group,the serum ALT,AST,ET-1 levels,MDA content and the expression of HIF-1 a were markedly decreased in group B,while the SOD activity significantly increased (P ＜ 0.05).And the pathologic changes were less severe in group B.Conclusion The high-dose fasudil markedly lessened the expression of HIF-1a,up-regulated the concentration of SOD,and lowered the levels of MDA and ET-1,protecting against heoatic ischemia/reperfusion injury in rats with liver cirrhosis.