| Project/Area Number |
14571449
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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 | Oita University (2004)
大分医科大学 (2002-2003) |
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Principal Investigator |
NOGUCHI Takayuki OITA UNIVERSITY, DEPT.OF ANESTHESIOLOGY, PROFESSOR, 医学部, 教授 (90156183)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Masakazu OITA UNIVERSITY, LECTURER, 医学部, 講師 (20220022)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | acid-induced lung injury / ventilator-induced lung injury VILI / HSP-70 / mild hypothermia / ICAM-1 / Urinastatin / 低・高体温 / HSP-70 / TNF-α / 低体温 / 炎症性サイトカイン / NF-κB / 急性肺障害モデル / 血液ガス / 気道内圧 |
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| Research Abstract |
Recent studies have clarified that mechanical stretching and pressure overload can induce lung injury and HSP70 in some tissues and cells. However, it remains unclear whether HSP70 is induced in stretch-subjected lungs, such as those under mechanical ventilation. The present study was designed to investigate the effects of high peak airway pressure(PAP) ventilation on HSP70 expression in intact rat lungs. Male Sprague-Dawley rats were randomly allocated to one of three groups : non-ventilated(anesthesia alone) control group(NVC) ; PAP 15 cmH_2O group(P15) ; and PAP 30 cmH_2O group(P30). Following the 30 min of pressure-controlled assisted ventilation, HSP70 expression in the P30 group was significantly upregulated in bronchiolar cells and subepithelial tissues at 12 h and this upregulation continued throughout the observation period. In contrast, there were no significant differences between the NVC and P15 groups, although HSP70 was upregulated in the P15 group at all time points. HSP
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70 was induced by high PAP ventilation, but its specific role and induction mechanism remain unclear.
Next he effects of mild hypothermia were studied on the expression of intercellular adhesion molecule-1(ICAM-1) and the accumulation of neutrophils after acid-induced lung injury in the rat. Oxygenation in acid-instilled rats was significantly impaired as compared to that in non-instilled groups, but induction of mild hypothermia gradually improved oxygenation. Expression of ICAM-1 was enhanced in the acid-instilled normothermic group. By contrast, no overexpression of ICAM-1 and its transcript was detected in the acid-instilled hypothermic group. In addition, accumulation of neutrophils was markedly inhibited after exposure to mild hypothermia irrespective of the instillation of acid. Our data suggest that mild hypothermia can inhibit the adhesion, activation, and accumulation of neutrophils in the acute phase of acid-induced lung injury and suggest an approach that might potentially reduce ongoing damage in patients with ARDS.
Finally we studied effects of human urinary trypsin Inhibitor(Urinastatin UTI) on acid-induced lung injury. UTI is known to inhibit production of tumor necrosis factor(TNF)-a, which potently stimulates leukocyte activation. The purpose of this study was to clarify whether UTI improves acid-induced lung injury in rats by inhibiting activated leukocytes via TNF-aproduction. UTI significantly improved the OA-induced histological changes for 4 h after OA administration. The OA-induced reduction of PaO2, the increase of pulmonary vascular permeability, and the levels of MPO activity and TNF-a in lung tissues weresignificantly improved in rats administrated UTI. The effects in the leukocytopenia group were similar to those in the UTI-administered group. Less
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