Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Family Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
BMJ Open Respir Res. 2021 Jul;8(1). doi: 10.1136/bmjresp-2021-000879.
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.
To develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.
Rats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO), 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.
The current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO 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.
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.
急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）是一种致死性疾病，治疗选择有限，死亡率高得令人无法接受。了解 ALI/ARDS 发展过程中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、可重复的纯 SI 动物模型可用于研究 ALI/ARDS 的治疗选择，而不会引入皮肤烧伤或其他病理学的混杂变量。
开发一种纯 SI 诱导的 ALI 小动物模型，并使用该模型最终测试用于 ALI 的新型治疗方法。
使用定制的烟雾发生器使大鼠暴露于烟雾中。在 SI 前后测量外周血氧饱和度（SpO）、心率、动脉血气和胸部 X 射线（CXR）。对健康和 SI 动物的肺组织进行湿/干重（W/D）比、肺损伤评分和切割型半胱氨酸蛋白酶 3 的免疫组织化学染色。
本研究表明，SI 后大鼠发生 ALI，表现为 SpO 显著持续下降和 CXR 上弥漫性双侧肺浸润。与健康动物相比，SI 动物的肺组织显示出炎症、水肿和细胞凋亡增加，表现为 W/D 比、损伤评分和收获组织中切割型半胱氨酸蛋白酶 3 水平增加。
我们成功地开发了一种纯 SI 诱导的 ALI 小动物模型。该模型提供给科学界，作为一种可靠的孤立性肺 SI 诱导损伤模型，没有皮肤损伤或其他全身病理学的混杂变量，可用于研究新型治疗方法或其他研究。
