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  • Title: Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray.
    Author: Morita T, Togo S, Kubota T, Kamimukai N, Nishizuka I, Kobayashi T, Ichikawa Y, Ishikawa T, Takahashi S, Matsuo K, Tomaru Y, Okazaki Y, Hayashizaki Y, Shimada H.
    Journal: J Hepatobiliary Pancreat Surg; 2002; 9(3):352-9. PubMed ID: 12353146.
    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.
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