A diversified approach to investigate the mechanism of acute lung injury and to establish its therapeutic strategy

多种方法研究急性肺损伤的机制并制定其治疗策略

• 批准号: 23592303
• 负责人: KURAHASHI Kiyoyasu
• 金额: $ 3.33万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592303/
• 关键词: 急性肺傷害; HIF-1; 肺胞上皮細胞; ARDS; TLR-4; アポトーシス; FasL; 急性肺障害; KGF; Fas; エンドトキシン; サイトカイン; 肺上皮細胞

We found that pro-inflammatory cytokines are secreted in non-ventilated lungs during one-lung ventilation, while these cytokines were reduced when continuous positive airway pressure (CPAP) was applied in the non-ventilated lungs. Application of CPAP to non-ventilated lungs during one-lung ventilation would be a prophylactic approach for post-operative lung injury.These concepts may be generalized to ventilator strategies during acute respiratory distress syndrome (ARDS). The application of high positive end-expiratory pressure (PEEP) would be of benefit not only to improve arterial partial oxygen tension but also to ameliorate lung inflammation and concomitant lung injury by preventing lung tissue hypoxia. In addition, we found that hypoxia inducible factor (HIF)-1 reduces the inflammation, typical for TNF-alpha up-regulation during experimental hypoxemia in vivo and in vitro. It is suggested that activation of HIF-1 would be a potential therapeutic approach for lung injury.

我们发现，在单肺通气时，非通气肺分泌促炎细胞因子，而在非通气肺应用持续正压(CPAP)时，这些细胞因子的分泌减少。将CPAP应用于单肺通气时的非呼吸机肺，将是预防术后肺损伤的一种方法。这些概念可推广到急性呼吸窘迫综合征(ARDS)期间的呼吸机策略。高呼气末正压(PEEP)的应用不仅有利于改善动脉血氧分压，而且可以通过防止肺组织缺氧来减轻肺部炎症和伴随的肺损伤。此外，我们还发现低氧诱导因子(HIF)-1可以减轻炎症，这是体内和体外实验性低氧血症时肿瘤坏死因子-α上调的典型表现。提示HIF-1的激活可能成为肺损伤治疗的一种新途径。

项目成果

分離肺換気中の非換気側肺において無気肺に伴う低酸素が炎症を惹起する．

与肺不张相关的缺氧会在隔离肺通气期间导致非通气肺发生炎症。

• 发表时间: 2013
• 作者: 東條健太郎;長嶺祐介;矢澤卓也;後藤隆久;倉橋清泰
• 通讯作者: 倉橋清泰

Hypoxia-inducible factor-1 is up-regulated in hypoxia-induced lung injury and acts as anti-inflammatory transcription factor in lung epithelial cells

缺氧诱导因子-1 在缺氧诱导的肺损伤中上调，并在肺上皮细胞中充当抗炎转录因子

• 发表时间: 2014
• 作者: Tojyo K;Nagamine Y;Ota S;Baba Y;Goto T;Kurahashi K
• 通讯作者: Kurahashi K

無気肺における肺胞低酸素は肺傷害を引き起こす

肺不张肺泡缺氧导致肺损伤

• 发表时间: 2014
• 作者: 東條健太郎;長嶺祐介;矢澤卓也;水原敬洋;後藤隆久;倉橋清泰
• 通讯作者: 倉橋清泰

Hypoxia-inducible factor-1 is up-regulated in hypoxia-induced lung injury and acts as anti-inflammatory transcription factor in lung epithelial cells.

缺氧诱导因子-1 在缺氧诱导的肺损伤中上调，并在肺上皮细胞中充当抗炎转录因子。

• 发表时间: 2014
• 作者: Tojo K;Nagamine Y;Ota S;Baba Y;Goto T;Kurahashi K
• 通讯作者: Kurahashi K

分離肺換気中の虚脱肺へのCPAP付加は肺の炎症を軽減する

在肺隔离通气期间对塌陷的肺进行 CPAP 治疗可减少肺部炎症

• 发表时间: 2012
• 作者: 東條健太郎;大田周平;馬場靖子;古賀資和;後藤隆久;倉橋清泰
• 通讯作者: 倉橋清泰