| Project/Area Number |
19591795
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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, 岡山大学病院, 准教授 (40252952)
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| Co-Investigator(Kenkyū-buntansha) |
MORIMATSU Hiroshi 岡山大学, 岡山大学病院, 助教 (30379797)
MORITA Kiyoshi 岡山大学, 大学院・医歯薬学総合研究科, 教授 (40108171)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 周術期管理学 / 炎症 / 出血性ショック / 急性肺障害 / 一酸化炭素 / 急性肺傷害 / 好中球 / 吸入療法 / 炎症性メディエーター / 治療効果 / ヘムオキシゲナーゼ-1 / ヘム / 転写因子 / TNF-α / iNOS |
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| Research Abstract |
Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of the present study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats. Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30mmHg for 60min followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were maintained either in room air, or exposed to CO at 250ppm for 1 hour before and 3 hours after HSR. HSR caused an increase in the DNA binding activity of nuclear factor (NF)-κB and activator protein 1 (AP-1) in the lung followed by the upregulation of pulmonary gene expression of tumor necrosis factor-α, inducible nitric oxide synthase and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet-weight to dry-weight ratio in the lung, and more prominent histopathological changes including congestion, edema, cellular infiltration and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histological changes, less upregulation of inflammatory mediators and less activation of NF-κB and AP-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases of mRNA expression of IL-10 in the lung. These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by upregulation of anti-inflammatory IL-10.
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