| Project/Area Number |
17591345
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
KAWACHI Shigeyuki Keio University, School of Medicine, assistant, 医学部, 助手 (80234079)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Hirotomo Keio University, School of Medicine, assistant, 医学部, 助手 (00348658)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | HMGB-1 / Hepatic ischemia-reperfusion injury / Liver transplantation / Cytokine / 肝虚血再灌流障害 |
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| Research Abstract |
(Aim)
The aim of this study was to investigate the role of HMGB-1 in hepatic ischemia-reperfusion injury in rat.
(Material and Method)
Seventy percent hepatic ischemia-reperfusion injury was induced for 60 min in Wistar male rats. Serum HMGB-1 was measured using ELISA assay by time after reperfusion. Between the non-treatment group (control group) and the anti-HMGB-1 polyclonal antibody treatment group (treatment group), the following findings were compared ; AST/ALT levels after reperfusion, histological damage by hematoxylin and eosin (H.E.) staining, HMGB-1 localization by immunohistochemistry using anti-HMGB-1 monoclonal antibody.
(Results)
AST/ALT levels were increased dramatically 3 to 6 hour after reperfusion and remained high levels until 24 hour after reperfusion.. Serum HMGB-1 levels were also significantly increased 6 to 9 hour after reperfusion. AST/ALT levels were significantly improved after 24 hour after reperfusion in treatment group compared to control group. Histological damage was also dramatically improved in treatment group 24 hour after reperfusion compared to control group. Immunohistochemistry revealed that HMGB-1 positive staining was observed in nucleus of hepatocytes in treatment group. Whereas in control group, HMGB-1 positive stainings were observed in activated Kupper cells and neutrophils and diffuse positive stainings were also observed in necrotic tissue in rat liver.
(Conclusion)
These results suggested that HMGB-1 may play an important role in hepatic ischemia-reperfusion injury and anti-HMGB-1 antibody may be a strong therapeutic tool for reperfusion injury in clinical liver transplantation.
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