Abstract:

Objective To establish experimental model of acute on chronic liver failure in rats, describing the kinetic changes of serum TNF- ,IL-10 and hepatocytes apoptosis. Methods Immunological hepatic fibrosis was induced by human serum albumin injection in Wistar rats. In rats with fibrosis stage IV, D-galactosamine/lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours, respectively. Liver function parameters, serum TNF- ,IL-10 levels were measured after treatment with D-galactosamine/lipopolysaccharide, as well as liver pathology study. Cell apoptosis was detected by tunnel assay. Results 90% rats died from acute liver failure after administration of D-galactosamine /lipopolysaccharide, with mean survival time of (16.1 3.7) hours.Liver function tests were compatible with liver failure. Histopathology revealed massive or sunbmassive necrosis in regenerative nodules, while fibrosis septa were intact. Plasma level of TNF- significantly increased, in association with apoptosis, while profile of plasma IL-10 level was consistent with immunosuppression seen in patients with acute-on-chronic liver failure. Conclusion Experimental model of acute-on-chronic liver failure can be established successfully by administration of D-galactosamine/ lipopolysaccharide on the immunological-induced cirrhosis. TNF-mediated hepatocytes apoptosis may play very important role in the pathogenesis. This results indicated that early artificial liver or blood apheresis therapy which could remove inflammatory medium may be useful.

Key words: Animal model, Lipopolysaccharide, TNF-a