Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray

J Hepatobiliary Pancreat Surg. 2002;9(3):352-9. doi: 10.1007/s005340200039.

Abstract

Background/purpose: Excessive hepatectomy often causes fatal liver failure. We have reported that this is mainly mediated by apoptosis, characterized pathologically by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) assay-positive hepatocytes and a ladder pattern in DNA fragmentation assays.

Methods: To investigate the mechanism, we used cDNA microarray analysis to compare clearly differentiated rat partial hepatectomy (PHx) models (90% PHx, and 95% PHx). All 90% PHx rats survived, but the 95% PHx animals died of hepatic failure within 96 h. Remnant liver was obtained at four time points (1, 3, 12, and 24 h after PHx). After RNA extraction, two samples were labeled with different fluorescent dyes and hybridized to the Institute of Physical and Chemical Research (RIKEN) set of 18 816 full-length enriched mouse cDNA arrays. Scanning for fluorescent dye signals was performed, and the mRNA expression ratio of the two models was examined.

Results: Genes of the p21 cyclin-dependent kinase (CDK) inhibitor, Fas, interleukin (IL)-18, and many caspases were upregulated at 1 h after PHx in the 95% PHx group. On the other hand, genes of Bcl-2, heat shock proteins, and glutathione-S-transferase were downregulated.

Conclusions: We concluded that fatal hepatic failure after excessive hepatectomy was characterized by increased apoptosis and diminished liver regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Hepatectomy / adverse effects*
  • Liver Failure / etiology*
  • Liver Failure / genetics*
  • Liver Failure / physiopathology
  • Liver Regeneration / genetics*
  • Male
  • Mice
  • Models, Animal
  • Oligonucleotide Array Sequence Analysis
  • Postoperative Complications*
  • Rats
  • Rats, Wistar