Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray.
OBJECTIVE
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.
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006498:Hepatectomy / Q000009:adverse effects*; D017093:Liver Failure / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar