| Project/Area Number |
13671143
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Kyorin University |
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Principal Investigator |
KAWANO Toshio Kyorin University, Faculty of Medicine, Professor, 医学部, 教授 (10306673)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Eri Kyorin University, Faculty of Medicine, Assistant, 医学部, 助手 (70360104)
WATANABE Hiroshi Kyorin University, Faculty of Medicine, Assistant, 医学部, 助手 (50281332)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | HFO / CMV / TNF-alpha / IL-R / NF-kappaB / lung injury / surfactant / HFO / EMSA / サーファクタント欠乏 / TNFα / in situ hybridization / 免疫組織染色 |
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| Research Abstract |
Conventional mechanical ventilation (CMV) with intermittent positive pressure initiates and exacerbates lung injury. High-frequency oscillation (HFO) has been recognized as an effective ventilatory strategy to minimize lung injury in respiratory support. We did following studies to clarify the mechanism of lung injury induced by CMV,
1) The expression of TNF-alpha in the alveolar epithelial cells in surfactant-depleted lung model In surfactant-depleted lung, mechanical ventilation with CMV increased production of TNF-alpha in air space. We compared the expression of TNF-alpha in alveolar epithelial cells after ventilation with HFO and CMV. We showed that ventilation with CMV induces diffuse pulmonary epithelial expression of TNF-alpha but the expression of TNF-alpha was minimal with HFO in surfactant-depleted model.
2) Production of IL-8 during mechanical ventilation in a surfactant-depleted rabbit lung
We measured the level of IL-8 in the lavage fluid and in the lung after both ventilation methods. The values of IL-8 in lavage fluid and in the lung were significantly greater in CMV group than in HFO group. Immunohistochemistry of CMV group showed alveolar epithelial cells, alveolar macrophages and endothelial cells were strongly stained. In turn, the signals were weaker in lung cells of HFO group. We concluded that release of IL-8 might have an important role in lung injury in this model.
3) Activation of NF-kappaB
In lungs of HFOgroup, NF-kappaB activity was slight. In contrast, the activity of NF kappaB was increased markedly in the lung of CMV group. After removal of alveolar cells, the level of NF kappaB activity slightly increased in lungs of 4hr HFO compared with that of 4hr CMV. We thought that the source of the high level of NF kappaB might have been PMNs that had infiltrated the alveoli.
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