MILD HYPOTHERMIA ATTENUATES RAT ACID-INDUCED ACUTE LUNG INJURY MODEL

轻度低温减轻大鼠酸诱导的急性肺损伤模型

• 批准号: 12671481
• 负责人: NOGUCHI Takayuki
• 金额: $ 2.24万
• 依托单位: OITA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671481/
• 关键词: lung injury; mild hypothermia; ntercellular; adhesion molecule-1; acute respiratory distress syndrome; 好中球; 接着分子; ICAM-1

The pathophysiology of the acute phase of acid-induced lung injury has been elucidated. However, once acute respiratory distress syndrome (ARDS) develops, the mortality rate remains high and there is, as yet, no effective therapy. There are reports that application of mild hypothermia is an effective treatment for ARDS, but, at the tissue and the molecular level, there is no clear understanding of the factors that to the positive outcome of such treatment. We studied the effects of mild hypothermia 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.

酸诱导的肺损伤的急性期的病理生理学已经阐明。然而，一旦发生急性呼吸窘迫综合征（ARDS），死亡率仍然很高，而且目前还没有有效的治疗方法。有报道指出应用亚低温是治疗ARDS的有效方法，但在组织和分子水平上，对影响亚低温治疗效果的因素还没有明确的认识。本研究观察了亚低温对酸诱导肺损伤大鼠细胞间粘附分子-1（ICAM-1）表达及中性粒细胞聚集的影响。与非灌注组相比，酸灌注大鼠的氧合明显受损，但诱导轻度低温逐渐改善氧合。常温组ICAM-1表达增强。与此相反，在酸灌注低温组中未检测到ICAM-1及其转录本的过表达。此外，无论是否滴注酸，暴露于亚低温后，中性粒细胞的蓄积均受到明显抑制。我们的数据表明，亚低温可以抑制酸诱导的肺损伤急性期中性粒细胞的粘附，激活和积累，并提出了一种可能减少ARDS患者持续损害的方法。