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Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray
Author(s) -
Morita Tomoyuki,
Togo Shinji,
Kubota Toru,
Kamimukai Nobuyuki,
Nishizuka Itaru,
Kobayashi Takatoshi,
Ichikawa Yasushi,
Ishikawa Takashi,
Takahashi Shinji,
Matsuo Kenichi,
Tomaru Yasuhiro,
Okazaki Yasushi,
Hayashizaki Yoshihide,
Shimada Hiroshi
Publication year - 2002
Publication title -
journal of hepato‐biliary‐pancreatic surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 0944-1166
DOI - 10.1007/s005340200039
Subject(s) - tunel assay , terminal deoxynucleotidyl transferase , microbiology and biotechnology , apoptosis , biology , complementary dna , dna fragmentation , microarray , microarray analysis techniques , cyclin dependent kinase , liver regeneration , downregulation and upregulation , hepatectomy , andrology , gene expression , gene , programmed cell death , biochemistry , cell cycle , regeneration (biology) , medicine , surgery , resection
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.