title: [Role of hepatocellular apoptosis and mechanisms of liver injury in lipopolysaccharide-induced acute liver failure in D-galactosamine-sensitized rats].
abstract: OBJECTIVE
  To investigate the situation of hepatocellular apoptosis in D-galactosamine (D-GalN)-sensitized rats with lipopolysaccharide (LPS)-induced acute liver failure and the mechanisms of liver injury therein.
  
  
  METHODS
  Forty eight Wistar rats were randomly divided into 6 equal groups to be injected peritoneally with LPS (50 microg/kg) and D-GalN (300 mg/kg) (treatment groups) or normal saline of the same volume (control groups), and then were killed 6, 24, or 48 hours later. Blood samples were collected from the portal vein or vena cava inferior to detect the contents of serum alanine aminotransferase (ALT), livers were take out to detect the hepatocellular apoptosis by TUNEL assay or ultrastructural observations, and the expressions of iNOS, p53, and p21waf1/cip1 gene were detected by reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  The ALT levels of the treatment groups were all significantly higher than those of the corresponding control groups, with the peaks 24 hours after treatment. Transmission electron microscopy showed that apoptotic cells were rare in the control subgroups, but were abundant in the liver tissues of the treatment subgroups. The apoptotic indices of liver cells of the 6, 24, and 48 hours treatment subgroups were 7.3% +/- 1.5%, 71.8% +/- 10.3%, and 68.2% +/- 11.9% respectively, all significantly higher than those of the control groups (2.6% +/- 1.1%, all P < 0.05). The apoptotic index increased gradually along with the time, however, the apoptotic indices of the 24 and 48 hours treatment subgroups were not significantly different (P > 0.05). The mRNA expression levels of iNOS gene of the control subgroups, 6 hours treatment subgroup, 24 hours treatment subgroups, and 48 hours treatment subgroup were 0, 0.53 +/- 0.11, 0.36 +/- 0.08, and 0.15 +/- 0.04 respectively with a significant difference among different subgroups, and with a peak 6 hours after treatment. The p53 expressions of the control subgroups, 6 hours treatment subgroup, 24 hours treatment subgroups, and 48h treatment subgroup were 0.031 +/- 0.006, 0.022 +/- 0.008, 0.49 +/- 0.11, and 0.39 +/- 0.17 respectively, being low in both control subgroups and 6h treatment subgroup and significantly upregulated in the 24 and 48 hours treatment groups. Expression of p21waf1/cip1 was not detected in the control subgroups and 48 hours treatment subgroup, but was found in the 6 hours and 24 hours treatment subgroups, with a peak in the 24 hours treatment subgroup.
  
  
  CONCLUSIONS
  Acute liver failure can be induced by low dose LPS in D-GalN-sensitized rats, which may be associated with the early high expression of iNOS gene; Apoptosis is the important morphological feature in this process.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Molecular Medicine, Nanchang 330006, China.
authors.forename: Liang-ming
authors.initials: LM
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Ji-xiang
authors.initials: JX
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Deng
authors.forename: Shui-lin
authors.initials: SL
authors.lastname: Sun
authors.forename: Gao-fei
authors.initials: GF
authors.lastname: Xiong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005688:Galactosamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; D005688:Galactosamine