Recombinant human hepatocyte growth factor protects the liver against hepatic ischemia and reperfusion injury in rats

Background. Recent evidence indicates that hepatocyte growth factor (HGF) h as a cytoprotective effect against hepatic injury caused by hepatotoxins an d inflammatory cytokines. Studies were performed to determine whether HGF i nfluences the survival rate of rats subjected to hepatic warm ischemia/repe rfusion (WI/Rp) injury. Methods, Male Sprague-Dawley rats were subjected to total or segmental hepa tic ischemia by occluding the hepatic artery, portal vein, and bile duct wi th a microvascular clip. Rats were treated with four intravenous injections of recombinant human HGF (rhHGF 1 mg/kg) or the vehicle 72, 48, 24, and 12 h before surgery. Results. None of the eight animals in the control group were alive 12 h aft er total hepatic WI/Rp, Seven of eight animals in the rhHGF-treated group w ere alive more than 2 days after the reperfusion, In the model of segmental hepatic ischemia, rhHGF inhibited the increase in cytokine-induced neutrop hil chemoattractant in serum. The number of neutrophils infiltrating the li ver was significantly lower in the rhHGF-treated group than in the control group. rhHGF prevented increases in the activity of serum alanine transamin ase and in hepatic necrosis. Experiments with proliferating cell nuclear an tigen staining demonstrated that hepatocyte proliferation markedly increase d in rhHGF-treated rats as compared with controls. Conclusions. These results indicate that HGF facilitates recovery of the li ver from hepatic WI/Rp injury, at least in part through the prevention of n eutrophil infiltration and the activation of hepatocyte proliferation. (C) 2000 Academic Press.