MILD HYPOTHERMIA ATTENUATES RAT ACID-INDUCED ACUTE LUNG INJURY MODEL

酸性肺损伤急性期的病理生理学机制已经阐明。然而，一旦发生急性呼吸窘迫综合征(ARDS)，死亡率仍然很高，到目前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，对影响亚低温治疗效果的因素尚无明确的认识。我们研究了亚低温对酸诱导大鼠肺损伤后细胞间黏附分子-1(ICAM-1)表达和中性粒细胞聚集的影响。与非酸灌注组相比，酸灌注组大鼠的氧合能力明显受损，但亚低温的诱导逐渐改善了氧合能力。常温酸灌注组ICAM-1表达增强。而酸低温组未检测到ICAM-1及其转录本的过度表达。此外，中性粒细胞的积累在暴露于亚低温后明显受到抑制，而与酸的滴注无关。我们的数据表明，亚低温可以抑制酸性肺损伤急性期中性粒细胞的黏附、激活和聚集，并提出了一种可能减少ARDS患者持续损害的方法。

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.