title: [Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].
abstract: OBJECTIVE
  To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment.
  
  
  METHODS
  Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.
  
  
  RESULTS
  Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure.
  
  
  CONCLUSIONS
  We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.
authors.affiliation: Artificial Liver Treatment and Training Center, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Xu-hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Tai-ling
authors.initials: TL
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Li-jie
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Chen-zhao
authors.initials: CZ
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhong-ping
authors.initials: ZP
authors.lastname: Duan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005688:Galactosamine / Q000009:adverse effects; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D017114:Liver Failure, Acute / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000009:adverse effects*
chemical_list: D008070:Lipopolysaccharides; D012709:Serum Albumin; D005688:Galactosamine