| Project/Area Number |
16591813
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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 |
Emergency medicine
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| Research Institution | Yokohama City University Graduate School of Medicine |
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Principal Investigator |
KURAHASHI Kiyoyasu Yokohama City University, Graduate School of Medicine, Department of Anesthesiology and Critical Care, Associate professor, 医学研究科, 準教授 (50234539)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Kyota Yokohama City University Hospital, Department of Anesthesiology, Assistant professor, 附属病院, 助手 (00287731)
TATEDA Kazuhiro Toho University Faculty of Medicine, Department of Microbiology and Infectious Diseases, Associate professor, 医学部, 講師 (20236558)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | acute lung injury / ventilator induced lung injury / keratinocyte growth factor / lung protective strategy / gene therapy / reproduction / cytokines / hyperadc lung injury / レジオネラ肺炎 / 高濃度酸素 / 肺感染症 / 肺損傷 / レジオネラ / 肺炎 / 肺傷害 / 人工呼吸 / アポトーシス / ventilator induced lung injury |
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| Research Abstract |
We studied anesthetized and mechanically ventilated rats, in which the hepatic inflow was transiently interrupted twice for 15 minutes. Two tidal volumes, 6 ml/kg (IR-LT) and 24 ml/kg (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation (NC-LT and NC-HT, respectively). Of the 4 groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet to dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the BAL fluid TNF-α concentration. These findings suggest that liver ischemia-reperfusion caused systemic inflammation, and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.
Adenovirus-mediated transfer of keratinocyte growth factor (KGF) cDNA successfully expressed high level of KGF in airway epithelial cells, and consequently raised significant lung epithelial cell proliferation, improved oxygenation, and decreased mortality. Furthermore, there was minimal vector-associated inflammation. We suggest that KGF gene transduction into lungs is a promising potential treatment for acute lung injury and would be a useful tool for regeneration research.
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