2006 Fiscal Year Final Research Report Summary
Development of the new strategy for acute renal failure by modulating the signal transduction
| Project/Area Number |
16591542
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Okayama University |
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Principal Investigator |
TAKAHASHI Toru Okayama University, Okayama University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (40252952)
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| Co-Investigator(Kenkyū-buntansha) |
MIZOBUCHI Satoshi Okayama University, Okayama University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (70311800)
MORITA Kiyoshi Okayama University, Graduate School of Medicine, Professor, 大学院医歯薬学総合研究科, 教授 (40108171)
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| Project Period (FY) |
2004 – 2006
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| Keywords | acute renal failure / acute lung injury / hemorrhagic shock / heme oxygenase-1 / stress protein / inflammation / apoptosis / oxidative stress |
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| Research Abstract |
Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress which leads to acute lung injury. Heme oxygenase-1 (H0-1) (EC 1.14.99.3), the rate-limiting enzyme in heme catabolism, is inducible by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. In this study, we examined expression of HO-1 as well as tissue injuries in the lung, liver, and kidney after HSR in rats. We also pretreated animals with heme arginate (HA), a strong inducer of HO-1, and examined its effect on the HSR-induced lung injury. HO-1 expression significantly increased in the liver and kidney following HSR, while its expression in the lung was very low and unchanged after HSR. In contrast to HO-1 expression, tissue injury and tumor necrosis factor-a (TNF-a) gene expression was more prominent in the lung compared with those in the liver and kidney. HA pretreatment markedly induced HO-1 in pulmonary epithelial cells, and ameliorated the lung injury induced by HSR as judged by the improvement of histological changes, while it decreased TNF-a and inducible nitric oxide gene expression, lung wet weight to dry weight ratio, and myeloperoxidase activity. In contrast, inhibition of HO-1 by tin mesoporphyrin administration abolished the beneficial effect of HA pretreatment. These findings suggest that tissues with higher HO-1 may be better protected than those with lower HO-1 from oxidative tissue injury induced by HSR. Our findings also indicate that HA pretreatment can significantly suppress the HSR-induced lung injury by virtue of its ability to induce HO-1.
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