[Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].
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.
Liu
Xu-hua
XH
Artificial Liver Treatment and Training Center, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
Chen
Yu
Y
Wang
Tai-ling
TL
Lu
Jun
J
Zhang
Li-jie
LJ
Song
Chen-zhao
CZ
Zhang
Jing
J
Duan
Zhong-ping
ZP
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*
D008070:Lipopolysaccharides; D012709:Serum Albumin; D005688:Galactosamine