The protective effects of different doses of fasudil on hepatic ischemia/reperfusion injury in rats with cirrhosis

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 (CCl4) 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-1a 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 hepatic ischemia/reperfusion injury in rats with liver cirrhosis. Key words: Liver cirrhosis, experimental; Reperfusion injury; Fasudil