Analysis of mechanisims of the ischemia-reperfusion injury of the liver using cDNA microarray

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671323
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yokohama City University
• Principal Investigator: MIURA Yasuhiko Yokohama City University Hospital, Assistant, 医学部, 助手 (50326055)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Hiroshi Yokohama City University, Professor, 医学研究科, 教授 (90117747) ; TOGO Shinji Yokohama City University, Assistant Professor, 医学研究科, 助教授 (10244477) ; SEKIDO Hitoshi Yokohama City University Hospital, Instructor, 医学研究科, 講師 (90187849) ; OKAZAKI Yasushi RIKEN Genomic Science Center (GSC), Laboratory for Genome Exploration Research Group, Team Leader, ゲノム科学総合研究センター, チームリーダー (80280733) ; HAYASHIZAKI Yoshihide RIKEN Genomic Science Center (GSC), Laboratory for Genome Exploration Research Group, Project Director, ゲノム科学総合研究センター, プロジェクトディレクター (70192705)
• Project Period (FY): 2001 – 2003
• Keywords: Ischemia-reperfusion injury of the liver / Prostaglandin E_1 / Heat-shock protein / Preconditioning / Apoptosis

Research Abstract

Background. Prostaglandin E_1 (PGE_1) has several potential therapeutic effects including cytoprotection, vasodilatation and inhibition of platelet aggregation. This study investigates the protective mechanism of PGE_1 against hepatic ischemia-reperfusion injury in vivo using cDNA microarray.
Methods. PGE_1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic (about 70% ischemia of the whole liver) for 30 min and then reperfused. Livers were harvested at 0, 10, and 30 min after reperfusion. Messenger RNA was extracted and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse cDNA microarray.
Results. Serum ALT and AST levels at 180 min after reperfusion were significantly lower in the PGE_1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes for heat-shock protein 70, glucose-regulated protein 78, heat-shock protein 86 and glutathione S-trans ferase were up-regulated at 0 min after reperfusion in the PGE_1 group.
Conclusions. The present study suggested that PGE_1 induces the heat-shock proteins immediately after ischemia-reperfusion. Heat-shock proteins may play an important role in the ameliorate effects of PGE_1 against ischemia-reperfusion injury of the liver.