Zhao Mengjia, Wang Bixu, Zhou Fangmei, Fang Chengnan, Zhu Bingqi, Zhou Mingyuan, Ye Xiaoqing, Chen Yuchi, Ding Zhishan
School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Ningbo Yinzhou Center for Disease Control and Prevention, Ningbo, 315199, China.
Inflammation. 2024 Aug 30. doi: 10.1007/s10753-024-02136-w.
Severe pneumonia is one of the most common critical diseases in clinical practice. Existing models for severe pneumonia have limitations, leading to limited clinical translation. In this study, a two-hit severe pneumonia mouse model was established by inducing primary pneumonia through intratracheal instillation of 800 μg lipopolysaccharide (LPS), followed by intraperitoneal injection of 10 mg/kg LPS. The effectiveness of various inflammatory indicators and the lung tissue damage during the time course of this model were confirmed and evaluated. At 3 h post two-hit, the IL-6, TNF-α levels in peripheral blood and bronchoalveolar lavage fluid (BALF), and the white blood cells, neutrophils, and lymphocytes in BALF notably exhibited the most pronounced elevation. At 12 h post two-hit, the white blood cells and neutrophils in peripheral blood significantly increased, accompanied by notable alterations in splenic immune cells and worsened pulmonary histopathological damage. Transcriptomics of lung tissue, microbiota analysis of lung and gut, as well as plasma metabolomics analyses further indicated changes in transcriptional profiles, microbial composition, and metabolites due to the two-hit modeling. These results validate that the two-hit model mimics the clinical presentation of severe pneumonia and serves as a robust experimental tool for studying the pathogenesis of severe pneumonia and developing and assessing treatment strategies.
重症肺炎是临床实践中最常见的危重病之一。现有的重症肺炎模型存在局限性，导致临床转化有限。在本研究中，通过气管内注入800μg脂多糖（LPS）诱导原发性肺炎，随后腹腔注射10mg/kg LPS，建立了双打击重症肺炎小鼠模型。确认并评估了该模型病程中各种炎症指标的有效性和肺组织损伤情况。双打击后3小时，外周血和支气管肺泡灌洗液（BALF）中的IL-6、TNF-α水平，以及BALF中的白细胞、中性粒细胞和淋巴细胞显著升高最为明显。双打击后12小时，外周血中的白细胞和中性粒细胞显著增加，同时脾免疫细胞出现明显变化，肺组织病理损伤加重。肺组织转录组学、肺和肠道微生物群分析以及血浆代谢组学分析进一步表明，双打击建模导致转录谱、微生物组成和代谢产物发生变化。这些结果证实，双打击模型模拟了重症肺炎的临床表现，是研究重症肺炎发病机制以及开发和评估治疗策略的有力实验工具。
