Abstract：
Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.
摘要：
香烟烟雾通过招募炎症细胞在肺部诱导炎症反应，导致肺癌等肺部疾病，慢性阻塞性肺疾病,和肺纤维化。用于评估香烟烟雾的不利影响的现有吸入暴露方法需要昂贵的设备并且是劳动密集型的。因此,我们试图开发一种新的方法,通过气管内滴注(ITI)整支香烟烟雾冷凝物(WCSC)来评估这些不良反应.使用自动视频滴注器通过ITI每天一次施用WCSC(0、5、10或20mg/mL),持续6或12天。反复WCSCITI增加了肺重量，和单核细胞趋化蛋白-1（MCP-1），中性粒细胞,与对照组相比，支气管肺泡灌洗液中的淋巴细胞水平。在肺组织的组织病理学分析中，在20mg/mLWCSC暴露6天和12天组中观察到轻度炎症反应.全基因组RNA-seq表达模式显示炎症和免疫反应相关基因,如趋化因子信号通路，Th1/Th2细胞分化，和细胞因子-细胞因子受体相互作用，在WCSC暴露后使用。此外,MCP-1是时间依赖性的，与对照组相比，在10mg/mL暴露组中MCP-1增加。这些结果表明WCSC可能诱导潜在的肺部炎症反应。此外，我们提出ITI可能是一种快速有效的方法来评估WCSC在短时间内（少于2周）的不良反应，它可以用来评估香烟吸入毒性研究作为一种替代方法。
