Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Am J Physiol Lung Cell Mol Physiol. 2020 Sep 1;319(3):L471-L480. doi: 10.1152/ajplung.00241.2020. Epub 2020 Jul 22.
Smoke inhalation injury increases morbidity and mortality. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. The goal of our research was threefold: ) to develop a reproducible survival model of smoke inhalation injury in rats that closely resembled our previous mouse model, ) to validate the rat smoke inhalation injury model using a variety of laboratory techniques, and ) to compare and contrast our rat model with both the well-established mouse model and previously published rat models to highlight our improvements on smoke delivery and lung injury. Mice and rats were anesthetized, intubated, and placed in custom-built smoke chambers to passively inhale woodchip-generated smoke. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for confirmatory tests. Lung sections were hematoxylin and eosin stained, lung edema was assessed with wet-to-dry (W/D) ratio, and inflammatory cell infiltration and cytokine elevation were evaluated using flow cytometry, immunohistochemistry, and ELISA. We confirmed that our mouse and rat models of smoke inhalation injury mimic the injury seen after human burn inhalation injury with evidence of pulmonary edema, neutrophil infiltration, and inflammatory cytokine elevation. Interestingly, rats mounted a more severe immunological response compared with mice. In summary, we successfully validated a reliable and clinically translatable survival model of lung injury and immune response in rats and mice and characterized the extent of this injury. These animal models allow for the continued study of smoke inhalation pathophysiology to ultimately develop a better therapeutic.
烟雾吸入性损伤会增加发病率和死亡率。为了持续研究吸入性损伤的病理生理学和治疗方法的开发，临床相关的动物模型是必要的。我们的研究目标有三个：1）开发一种与我们之前的小鼠模型相似的大鼠烟雾吸入性损伤可重复的生存模型；2）使用各种实验室技术验证大鼠烟雾吸入性损伤模型；3）比较和对比我们的大鼠模型与已建立的小鼠模型和之前发表的大鼠模型，突出我们在烟雾输送和肺损伤方面的改进。将小鼠和大鼠麻醉、插管并放入定制的烟雾室中，使其被动吸入木屑产生的烟雾。收集支气管肺泡灌洗液（BALF）和肺组织进行确认测试。用苏木精和伊红染色肺组织切片，通过湿重/干重（W/D）比评估肺水肿，使用流式细胞术、免疫组织化学和 ELISA 评估炎症细胞浸润和细胞因子升高。我们证实，我们的烟雾吸入性损伤小鼠和大鼠模型模拟了人类烧伤吸入性损伤后出现的损伤，有肺水肿、中性粒细胞浸润和炎症细胞因子升高的证据。有趣的是，与小鼠相比，大鼠的免疫反应更为严重。总之，我们成功地验证了一种可靠的、可临床转化的肺损伤和免疫反应大鼠和小鼠生存模型，并描述了这种损伤的严重程度。这些动物模型允许对烟雾吸入病理生理学进行持续研究，最终开发出更好的治疗方法。
