Background Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology. Objective To develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI. Methods Rats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals. Results The current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals. Conclusion We have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation. Data are available upon reasonable request from the corresponding author.

中文翻译：

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烟雾吸入性急性肺损伤大鼠模型

背景 急性肺损伤 (ALI)/急性呼吸窘迫综合征 (ARDS) 是一种致命疾病，治疗选择有限，死亡率高得令人无法接受。了解 ALI/ARDS 发展中涉及的复杂病理生理过程对于开发新的治疗策略至关重要。烟雾吸入 (SI) 损伤是烧伤相关 ALI/ARDS 患者发病率和死亡率的主要原因；然而，据我们所知，很少有可靠的、可重复的模型可用于纯 SI 动物模型来研究 ALI/ARDS 的治疗选择，而没有皮肤烧伤或其他病理学引入的混杂变量。目的开发纯 SI 诱导的 ALI 小动物模型，并使用该模型最终测试 ALI 的新疗法。方法 使用定制的烟雾发生器将大鼠暴露于烟雾中。在 SI 前后测量外周血氧饱和度 (SpO2)、心率、动脉血气和胸部 X 线 (CXR)。对健康和 SI 动物采集的肺组织进行湿/干重 (W/D) 比、肺损伤评分和裂解的 caspase 3 的免疫组织化学染色。结果 目前的研究表明 SI 后大鼠 ALI 的诱导，表现为 SpO2 的显着、持续降低和 CXR 上弥漫性双肺浸润的发展。与健康动物相比，暴露于 SI 的动物的肺组织显示出炎症、水肿和细胞凋亡增加，这反映在 W/D 比、损伤评分和收获组织的裂解 caspase 3 水平的增加上。结论 我们已成功开发出纯 SI 诱导的 ALI 小动物模型。该模型作为孤立的肺 SI 诱导损伤的可靠模型提供给科学界，没有皮肤损伤或其他系统病理学的混杂变量，可用于研究新疗法或其他调查。数据可根据通讯作者的合理要求提供。