| Project/Area Number |
08671424
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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 |
Digestive surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
SHIMIZU Koichi Kanazawa University, School of Medicine, Assistant Professor, 医学部, 講師 (30196513)
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| Co-Investigator(Kenkyū-buntansha) |
YAGI Masao Kanazawa University, University Hospital, Assistant Professor, 医学部・附属病院, 講師 (00182303)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | ischemia / reperfusion injury / cytokine / KF-kappaB / tyrosin kinase / JNK / apoptosis / liver / c-Jun N-terminal kinase / 肝虚血再灌流障害 / TNF-α / IL-6 / チロシンキナーゼ阻害剤 / ゲニステイン |
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| Research Abstract |
One of the most important complications after organ transplantation is graft damage caused by ischemia/reperfusion injury. The details of the mechanisms underlying organ injury under ischemia and reperfusion are not yet understood. We investigated the role of cytokines in mediating of ischemia/reperfusion injury and the intracellular signal transduction that modulates cytokine production.
The results from in-vitro experiments have shown that hypoxia induces the activation of NF-kappaB and tyrosine kinase inhibitors inhibits NF-kappaB activation by hypoxia. And the results from experiments using a mouse model for hepatic ischemia and reperfusion have shown that inflammatory cytokies affect liver injury following ischemia/reperfusion, and that pretreatment with a tyrosine kinase inhibitor, genistein, suppresses ischemia/reperfusion injury of the liver. Furthermore, it was also shown that JNK (c-Jun N-terminal kinase) was activated following hepatic ischemia and reperfusion. Interestingly, the activation of JNK and the number of apoptotic cells increased by shorter period of ischemia rather than longer period.
These results suggest that inhibition of cytokine production can suppress ischemia/reperfusion injury, and that JNK activation and apoptosis after short period of ischemia may play a protective role in tissue subjected to ischemia and reperfusion.
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