Mechanism research on the effects of fasudil to postoperative acute hepatic failure induced by hepatic ischemia hepatectomy on rats with obstructive jaundice

摘要

Objective:To establish a kind of animal model of postoperative acute hepatic failure induced by hepatic ischemia & hepatectomy on rats with obstructive jaundice, which could show similar clinical pathophysiological changes in hunman beings. To investigate the influence of fasudil to this model.Method:Selected 96 Wistar big rats as animal model of obstructive jaundice, which were treated with ligation and cuting off common bile duct. Rats in low-dose group were immediately injected fasudil of 10 mg/kg through portal vein after hepatectomy, while rats in high-dose group were immediately injected fasudil of 30 mg/kg through portal vein after hepatectomy, rats in control group were immediately injected equivalent normal saline through portal vein after hepatectomy. To determine the serum ALT, AST, TBIL (tumor necrosis factor-α, TNF-α)and (interferon-γ, INF-γ) levels in postoperative rats with hepatic failure within 6 h; to determine the (superoxide dismutase, SOD) activity and (malondialdehyde, MDA) content in hepatic tissue; hepatic tissue HE staining to observe the pathological injury; to observe animal model 96 h of survival rate.Results:That Proceeding internal biliary drainage operation to rats after obstruction for 14 h, and blocking 70% of hepatic blood supply, excising remnant liver after 30 min was in accordance with criteria of hepatic failure animal, and was deserved to further research. Compared with control group, serum AST, ALT, TBIL, TNF-α, INF-γ levels decreased in fasudil treatment group, SOD activity increased in hepatic tissue, MDA content decreased, pathological injury in hepatic tissue reduced, rats 96 h of survival rate increased, and the effects of high-dose group were more obvious than that in low-dose group.Conclusion:A surgical hepatic failure model in rat was established, which showed similar clinical pathophysiological changes in hunman beings. In addition, we have found that fasudil possibly played a role of protection to hepatic failure through regulating the inflammatory response, Reducing hepatic lipid peroxidation and strengthening the removal of the free radicals.