| Project/Area Number |
07670683
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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 |
Respiratory organ internal medicine
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
TOGA Hirohisa Kanazawa Medical University, Division of Respiratory Disease Department of Internal Medicine, Associate Professor, 医学部, 助教授 (90142554)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Masafumi Kanazawa Medical University, Division of Respiratory Disease Department of Inter, 医学部, 講師 (30165831)
OKAZAKI Hiroshi Kanazawa Medical University, Division of Respiratory Disease Department of Inter, 医学部, 助手 (70267730)
ISHIGAKI Masanobu Kanazawa Medical University, Division of Respiratory Disease Department of Inter, 医学部, 助手 (10247439)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | acute lung injury / dexamethasone / inducible nitric oxide synthase / endotoxin / immuno-histological stain / western blotting / RT-PCR / in situ hybridization / ウェスタンブロット / 成人呼吸窮迫症候群 / 一酸化窒素 / 肺高血圧 / 気管支肺胞洗浄 / 肺微小血管圧 / 酵素抗体法 |
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| Research Abstract |
(1) We administered endotoxin of 1 mg/kg body weight into the right ventricle in rats. Histopathology of the lungs showed mononuclear cell infiltration in the interstitium and alveolar edema 6, 12, 24 and 48 hour later. Western blotting (WB) of lung homogenate of 6 hour later revealed expression of inducible nitric oxide synthase (iNOS) protein.
(2) Immuno-histological stain of the lung showed expression of iNOS protein on 60 to 70% of alveolar type II cells and on a small number of alveolar macrophages. WB of both the whole lung and isolated type II cells showed iNOS band of 130 kD.There was no expression of iNOS protein in untreated lungs.
(3) Expression of iNOS mRNA of 360 bps was observed on RT-PCR for the whole lung and isolated type II cells. In situ hybridization for type II cells revealed a positive signal to anti-sence riboprobe for iNOS mRNA.There were no signals to sence riboprobe for iNOS mRNA, indicating specificity of the process.
(4) We determined the effect of intra-peritoneal administration of dexamethasone (4mg/kg wt) 12 hour before endotoxin on expression of iNOS protein in the lung by immuno-histological stain. Expression of iNOS protein on type II cells was suppressed in dexamethasone-treated lungs. Dexamethasone also inhibited expression of iNOS protein on isolated type II cells.
(5) In summary, there was expression of iNOS protein on alveolar type II cells in in vivo endotoxin-induced lung injury, which was regulated at the transcription phase, and dexamethasone inhibited the iNOS expression.
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