不同途径吸入脂多糖致大鼠急性肺炎模型的优选

Selection of Acute Pneumonia Rat Models Induced by Lipopolysaccharide with Different Inhalation Pathways

目的：平行比较气管滴入、口咽吸入、经鼻滴入与雾化吸入脂多糖（LPS）诱导的大鼠急性肺炎模型的病理变化，筛选最佳诱导大鼠急性肺炎的造模方法，并对其进行多指标验证。方法：气管滴入LPS组、口咽吸入LPS组、经鼻滴入LPS组、雾化吸入LPS组大鼠造模24h后，通过病理学观察各组肺组织炎症程度；雾化吸入LPS-I组，LPS-2组，LPS-3组依次造模24，16，8h后，采用无创气道动力学研究系统检测大鼠的肺功能，全自动血液分析仪对支气管肺泡灌洗液（BALF）中白细胞进行分类和计数；通过酶联免疫吸附测定法（ELISA）检测BALF及肺组织中的白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的含量；病理学观察各组大鼠肺组织的炎症程度。结果：与气管滴入、口咽吸入、经鼻滴入相比，雾化吸入LPS组大鼠肺部损伤程度一致，病理变化表现稳定，组内差异小。雾化吸入LPS多指标检测显示，与阴性组比较，造模后大鼠的呼吸频率（F），潮气量（TV），特殊气道阻力（sRaw）发生显著变化（P〈0．01，P〈0．05）；大鼠雾化LPS后8h时白细胞计数（WBC）增加；16h时WBC明显增加（P〈0．05），嗜中性粒细胞比例也开始增加（P〈0．01）；24b时WBC数目显著升高（P〈0．01），淋巴细胞所占比例开始显著升高（P〈0．05）；雾化吸入LPS后8h开始，BALF和组织中炎症阂子TNF-α及IL-6的含量均显著升高（P〈0．05，P〈0．01）。结论：雾化吸入LPS所致的大鼠肺部损伤程度一致，病理变化表现稳定，接近于临床急性肺炎的发展情况，有利于筛诜治疗角件肺餐的药物．

Objective： By comparing the pathological changes of rat pneumonia model induced by lipopolysaceharide （LPS）, which was given through tracheal instillation, oropharyngeal inhalation, nasal instillation and aerosol inhalation method, we screened out the best method to induce acute pneumonia in rats and verified it with multi-index. Method： At 24 h after modeling, inflammation degree of lung tissue of rats in each group was observed. While aerosol inhalation group （LPS-1, LPS-2 and LPS-3） have been modeled 24, 16, 8 h,respectively; lung function of rats in these three groups tested by non-invasive airway mechanics system, the white blood cells in bronchoalveolar lavage fluid （BALF） was classified and counted by automatic hematology analyzer, the contents of interleukin-6 （IL-6） and tumor necrosis factor-a （TNF-o~） in BALF and lung tissue were detected by enzyme linked immunosorbent assay （ELISA）. Furthermore, we observed the inflammation degree of lung tissue of rats in each group. Result： Compared with intratracheal instillation, oropharyngeal inhalation and nasal instillation, the degree of lung injury in rats from aerosol inhalation LPS group was consistent, the pathological changes were stable, and the differences in the group were small. At 8 h after modeling, the lung function of rats started to change, the contents of white blood cell count （WBC） began to increase in BALF, the contents of IL-6 and TNF-α in BALF and lung tissue began to increase. At 16 h, WBC increased significantly （P 〈 O. 05） , and the proportion of neutrophils began to increase obviously （P 〈 0.01 ）. At 24 h, WBC increased significantly （P 〈 0.01 ）, and the proportion of lymphocytes began to increase obviously （P 〈 0.05 ）. Conclusion： The animal model established by aerosol inhalation of LPS, which not only has a wide range of inflammation, but also distributes uniformly, furthermore, this model is close to the development of clinical acute pneumonia. In a conclusion, the pneumonia model established by aerosol inhalation of LPS is beneficial for the screening of drugs on pneumonia.