脂多糖诱导的小鼠鼻息肉动物模型研究

The characteristics of a mouse model with nasal polyps established by lipopolysaccharide

目的:探讨采用革兰阴性细菌产物脂多糖(LPS)建立小鼠鼻息肉动物模型的可行性及其特征,进一步揭示革兰阴性细菌在鼻息肉中的致病作用和可能的机制。方法:6~8周C57BL/6J小鼠鼻腔滴入5μg或10μg LPS(LPS组),建立鼻息肉动物模型。对照组小鼠鼻腔滴入无菌生理盐水。食物小球埋藏实验评估小鼠嗅觉功能。苏木精-伊红染色、中性粒细胞过氧化物酶(MPO)和嗅觉标记蛋白(OMP)免疫组织化学检测观察小鼠鼻黏膜组织病理学改变。用ELISA检测鼻腔灌洗液中细胞因子IFN-γ、TNF-a、IL-6的表达水平。结果:和对照组小鼠相比,LPS组小鼠鼻腔鼻息肉形成,伴有明显的嗅觉功能障碍以及较多的MPO^+炎症细胞和显著减少的OMP^+,鼻腔灌洗液中显著增加的IFN-γ、TNF-a、IL-6蛋白水平,以高剂量LPS组更为明显(P<0.05)。结论:单独采用革兰阴性细菌产物LPS可以成功诱导小鼠鼻息肉形成,该息肉中炎症细胞以中性粒细胞为主,伴嗅觉功能障碍和显著增多的Th1相关细胞因子,该模型符合中国等亚洲人主要鼻息肉的特征。LPS可能是革兰阴性细菌在鼻息肉中的重要致病机制之一。

Objective：To explore the effect of lipopolysaceharide（LPS） on the formation of nasal polyps in mice and its mechanism. Method：Five or ten μg of LPS were dropped into the nasal cavities of six to eight-week C57BL/6J mice in order to establish animal models with nasal polyps. Buried food pellets experiment was used to assess olfactory function of mice. Hematoxylin-eosin staining, olfactory marker protein（OMP）, and myeloperoxidase（MPO） for neutrophil immunohistochemistry were used to observe histopathological changes in the nasal mu cosa. The expression levels of cytokines, such as interferon（IFN） - γ, tumor necrosis factor（TNF） -α, IL-6 in the nasal lavage fluid, were detected by ELISA. Result： Compared to the control group, mice in the LPS groups showed significant nasal polyp formation, olfactory dysfunction, more MPOt cells while less OMP＋ cells in the nasal mucosa, as well as increased significantly levels of IFN-γ, TNF-α, and IL-6 in the nasal lavage fluids（all P〈0.05）. Conclusion：LPS from Gram negative bacteria alone can induce the formation of nasal polyps in mice, characterized by more neutrophils, olfactory dysfunction, and increasing Thl eytokine. Therefore, this model is commensurate with the characteristics of primary nasal polyps found in China and other major Asian. The current study suggests that LPS may be one of the important pathogenesis of gram-negative bacteria in the nasal polyps.