Elucidation of therapeutic and anti-inflammatory effect of carbon monoxide inhalation against acute lung injury

阐明吸入一氧化碳对急性肺损伤的治疗和抗炎作用

• 批准号: 22591730
• 负责人: TAKAHASHI Toru
• 金额: $ 2.66万
• 依托单位: Okayama Prefectural University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591730/
• 关键词: 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; 急性肺傷害; 抗炎症性シグナル伝達; IL-10; PPAR-γ; 酸化ストレス; アポトーシス; activated caspase-3; TUNEL; 出血性ショック蘇生; サイトカイン; 好中球; 吸入療法

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.

即使在成功复苏后，失血性休克也经常引起肺部炎症，从而诱发急性肺损伤（ALI）。我们之前证明，在失血性休克和复苏（HSR）之前和之后吸入低浓度的 CO 可以改善 HSR 诱发的 ALI。由于其抗炎作用，在本研究中，我们仅在复苏后对相同的 ALI 模型施用 CO，并检查它是否对大鼠产生治疗作用且无不良事件。 HSR 诱导的 ALI，因为在 HSR 之前用 CO 治疗动物并不能预防 HSR，这是通过对动物放血以达到 30 mmHg 的平均动脉压，然后用取出的血液进行复苏来诱导的。炎症基因表达上调并增加肺部细胞凋亡率，这是通过观察到转移酶介导的 dUTP-荧光素阳性细胞数量的增加来确定的。异硫氰酸盐 (FITC)、缺口末端标记染色和活化的 HSR 也会导致显着的组织病理学损伤，包括充血、水肿、细胞浸润和出血，相比之下，复苏后吸入 CO 3 小时可显着改善这些炎症事件。通过减少组织学损伤、炎症介质和细胞凋亡来证明，CO 对肺损伤的保护作用与肺损伤的增加显着相关。过氧化物酶体增殖物激活受体（PPAR）-γ（一种肺部抗炎转录调节因子）的蛋白表达水平，此外，吸入 CO 不会影响 HSR 期间的血流动力学状态或组织氧合。 a low 对 HSR 诱导的 ALI 具有有效的治疗作用，并通过增加 PPAR-γ 蛋白表达来减弱炎症级联反应。

项目成果

Protective effect of carbon monoxide inhalation on lung injury after hemorrhagic shock/resuscitation in rats.

一氧化碳吸入对大鼠失血性休克/复苏后肺损伤的保护作用。

• 发表时间: 2010
• 作者: Kanagawa F; Takahashi T; Shimizu H; Morita K; et al
• 通讯作者: et al

エンドトキシン・自然免疫研究 １５

内毒素/先天免疫研究 15

• 发表时间: 2012
• 作者: 川西 進;高橋 徹;清水裕子;小坂順子;黒田浩佐;森松博史;森田潔
• 通讯作者: 森田潔

一酸化炭素

一氧化碳

• 发表时间: 2011
• 作者: 高橋徹;森松博史;川西進;清水裕子;森田潔
• 通讯作者: 森田潔

GLUTAMINE-INDUCED HEME OXYGENASE-1 PROTECTS AGAINST INTESTINAL TISSUE INJURY IN A RAT MODEL OFHEMORRHAGIC SHOCK

谷氨酰胺诱导的血红素加氧酶-1 可防止失血性休克大鼠模型中的肠组织损伤

• 作者: Toru Takahashi et al

Inhalation of Carbon Monoxide after Resuscitation Ameliorates Hemorrhagic Shock-Induced Lung Injury

复苏后吸入一氧化碳可改善失血性休克引起的肺损伤

• 发表时间: 2013
• 影响因子: 3.4
• 作者: Kawanishi; S; Takahashi T; Shimizu H; Omori E; Sato K; Matsumi M; Maeda S; Nakao A; Morimatsu H; Morita K.
• 通讯作者: Morita K.