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

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 thep21 cyclin-dependent kinase (CDK) inhibitor, Fas, interleukin (IL)-18, and manycaspaseswere upregulated at 1–h after PHx in the 95%PHx group. On the other hand, genes ofBcl-2, heat shock proteins, andglutathione-S-transferasewere downregulated. Conclusions We concluded that fatal hepatic failure after excessive hepatectomy was characterized by increased apoptosis and diminished liver regeneration.