2012 Fiscal Year Final Research Report
Elucidation of therapeutic and anti-inflammatory effect of carbon monoxide inhalation against acute lung injury
| Project/Area Number |
22591730
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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 Prefectural University |
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Principal Investigator |
TAKAHASHI Toru 岡山県立大学, 保健福祉学部, 教授 (40252952)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Kiyoshi 岡山大学, 大学院・医歯薬学総合研究科, 教授 (40108171)
SHIMIZU Hiroko 岡山大学, 医学部, 客員研究員 (80423284)
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| Project Period (FY) |
2010 – 2012
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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 |
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| Research Abstract |
Even after successful resuscitation, hemorrhagic shock frequently causes pulmonary inflammation that induces acute lung injury (ALI). We previously demonstrated that when CO is inhaled at a low concentration both prior to and following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced ALI in rats due to its anti-inflammatory effects. In the present study, we administered CO to the same model of ALI only after resuscitation and examined whether it exerted a therapeutic effect without adverse events on HSR-induced ALI, since treatment of animals with CO prior to HSR did not prevent lung injury. HSR were induced by bleeding animals to achieve a mean arterial pressure of 30 mmHg for 1 h followed by resuscitation with the removed blood. HSR resulted in the upregulation of inflammatory gene expression and increased the rate of apoptotic cell death in the lungs. This was determined from an observed increase in the number of cells positive for transferase-mediated dUTP-fluorescein isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR also resulted in prominent histopathological damage, including congestion, edema, cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h following resuscitation significantly ameliorated these inflammatory events, demonstrated by reduced histological damage, inflammatory mediators and apoptotic cell death. The protective effects of CO against lung injury were notably associated with an increase in the protein expression level of peroxisome proliferator-activated receptor (PPAR)-γ, an anti-inflammatory transcriptional regulator in the lung. Moreover, CO inhalation did not affect the hemodynamic status or tissue oxygenation during HSR. These findings suggest that inhalation of CO at a low concentration exerts a potent therapeutic effect against HSR-induced ALI and attenuates the inflammatory cascade by increasing PPAR-γ protein expression.
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[Journal Article] Inhalation of Carbon Monoxide after Resuscitation Ameliorates Hemorrhagic Shock-Induced Lung Injury2013
Author(s)
Kawanishi, S, Takahashi T, Shimizu H, Omori E, Sato K, Matsumi M, Maeda S, Nakao A, Morimatsu H, Morita K.
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Journal Title
Mol Med Rep
Volume: 7
Pages: 3-10
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[Journal Article] Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice2012
Author(s)
Kawakami T, Puri N, Sodhi K, Bellner L, Takahashi T, Morita K, Rezzani R, Tim Oury TD, and Abraham, NG.
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Journal Title
Int J Hypertens, Article ID 740203
Pages: 11
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[Journal Article] Responses to surgical stress after esophagectomy: Gene expression of heat shock protein 70, toll-like receptor 4, tumor necrosis factor-α and inducible nitric oxide synthase2010
Author(s)
Suzuki S, Morimatsu, H, Omori E, Shimizu H, Takahashi T, Yamatsuji T, Naomoto Y, Morita K.
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Journal Title
Mol Med Rep
Volume: 3
Pages: 765-769
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