| Project/Area Number |
62480133
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
INOUE Masayasu Kumamoto University Medical School, 医学部, 助教授 (80040278)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Katsutaka Kumamoto University, 医療技術短期大学部, 教授 (10040213)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | liver transplantation / reperfusion injury / reactive oxygens / free radicals / multiple organ system failure / superoxide dismutase / analbuminemia / 内皮細胞障害 / アルブミン / 酸素毒性 / 虚血 / 虚血再還流 |
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| Research Abstract |
Liver transplantation is an effective way to treat patients with severe liver injury. However, retansplantation of the liver is often required predominantly due to primary non-function of a graft. To study the mechanism by which the function of the graft is decreased after transplantation, we have established the method for liver transplantation between normal and analbuminemic mutant rats. when normal rat liver was transplanted to the mutant rat, albumin levels in the peripheral blood increased rapidly. However, transient occlusion of the portal vein followed by reflow was found to decrease hepatic transport functions for cholephilic organic anions. We synthesized a superoxide dismutase derivative that circulates bound to albumin and accumulates in a tissue whose local pH is decreased. Intravenous administration of the derivatized enzyme markedly inhibited the decrease in liver transport function caused by a transient occlusion of the portal vein. This suggests that reactive oxygen radicals might be involved in the pathogenesis of primary non-function of a graft. Thus, control of oxygen toxicity minimize the decrease in the function of a graft. The imjured-site-directed SOD derivative might provide an important method to protect functions of a graft.
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