MILD HYPOTHERMIA ATTENUATES RAT ACID-INDUCED ACUTE LUNG INJURY MODEL

酸致肺损伤急性期的病理生理机制已被阐明。然而，一旦出现急性呼吸窘迫综合征（ARDS），死亡率仍然很高，而且迄今为止还没有有效的治疗方法。有报道称，应用亚低温治疗ARDS是一种有效的治疗方法，但在组织和分子水平上，对影响亚低温治疗积极结果的因素还没有明确的认识。我们研究了亚低温对大鼠酸致肺损伤后细胞间粘附分子-1 （ICAM-1）表达和中性粒细胞积累的影响。与未灌注组相比，酸灌注组大鼠的氧合明显受损，但诱导亚低温逐渐改善氧合。正常灌酸组ICAM-1表达增强。相比之下，在低温灌酸组没有检测到ICAM-1及其转录物的过表达。此外，暴露于轻度低温后，中性粒细胞的积累被明显抑制，而与酸的灌注无关。我们的数据表明，在酸致肺损伤的急性期，亚低温可以抑制中性粒细胞的粘附、激活和积累，并提示一种可能潜在地减少ARDS患者持续损伤的方法。

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.