| Project/Area Number |
12671173
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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 |
TANABE Minoru Department of Surgery, Keio University School of Medicine, Teaching Staff, 医学部, 助手 (50197513)
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| Co-Investigator(Kenkyū-buntansha) |
WAKABAYASHI Go Department of Surgery, Keio University School of Medicine, Assistant Professor, 医学部, 講師 (50175064)
SHIMAZU Motohide Department of Surgery, Keio University School of Medicine, Assistant Professor, 医学部, 講師 (70124948)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | ischemia-reperfusion injury / liver transplantation / c-Jun N-terminal kinase (JNK) / tumor necrosis factor-α (TNF-α) / microcirculation / c-Jun N-terminal kinase(JNK) / 肝障害 / MAP kinase / 虚血再潅流障害 |
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| Research Abstract |
Patients with end-stage liver disease in Japan still depend on living-donor liver transplantation, since cadaveric organ donation is extremely rare. Because ischemia-reperfusion injury of the graft organ is inevitable in transplantation, control of ischemic injury enable us to use the organ safely from unsalable or nonheartbeating donor, leading to the improvement of organ shortage. We have been demonstrated the key role of tumor necrosis factor (TNF) and interleukin-1 in ischemia-reperfusion injury of the liver and small intestine. Recently, mitogen-activated protein kinase (MAPK) super family has been widely noticed as upupstream signal transduction mechanisms for TNF-α and IL-1β have been reported. Especially, c-Jun N-terminal kinase (JNK) induce cell apoptosis by various stimuli including ischemia, suggesting these enzymes play a key role in ischemia reperfusion injury. We investigated the activation of JNK during hepatic ischemia-reperfusion injury in the rat model.
Remarkable hemrrahgic necrosis was shown in the reperfused liver after 60-minute warm ischemia, and the mean serum AST increased over 2000 IU/L at 180 minutes after reperfusion, indicating that severe liver damage was induced. In vivo microfluorograph showed remarkable increase in leukocyte-endothelium interaction in sinusoids and venules of the reperfused liver. After reperfusion, tissue and serum TNF-α level increased over 6 folds, and tissue JNK activity increased by 12.5 folds, compared to the value before ischemia. These results suggest that JNK may play some role in the mechnism of ischemia reperfusion injury.
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