Wang Shuibin, Zhang Hanwu, Xi Zulian, Huang Jingjing, Nie Jun, Zhou Bin, Deng Yuqin, Tao Zezhang
Department of Otolaryngology-Head and Neck Surgery, Yichang Yiling Hospital, Yichang, Hubei 443100, P.R. China.
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Exp Ther Med. 2017 Dec;14(6):5275-5282. doi: 10.3892/etm.2017.5208. Epub 2017 Sep 27.
Research has identified that gram-negative bacteria have an important role in refractory nasal polyps. In the present study, lipopolysaccharide (LPS) was used to establish a mouse model with neutrophilic nasal polyps in order to explore the effect and mechanism of LPS on the formation of neutrophilic nasal polyps in mice. A total of 5 or 10 µg of LPS was dropped into the nasal cavities of C57BL/6J mice in order to establish animal models with neutrophilic nasal polyps. Histological staining, toll-like receptor 4 (TLR4), cluster of differentiation 68 for macrophages and myeloperoxidase for neutrophil immunohistochemistry were used to observe histopathological changes in the nasal mucosa. The expression levels of cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-17 in the nasal lavage fluid, were detected by ELISA. Compared with the control group, mice in the LPS groups exhibited significant mucosa epithelial cell damage and nasal polyp formation. Furthermore, TLR4 cells, macrophages, neutrophils and significantly increased levels of IFN-γ, TNF-α, and IL-17 in the nasal lavage fluids were indicated (all P=0.008). These findings indicated that LPS is able to activate the TLR4 receptor pathway to induce the formation of neutrophilic nasal polyps in mice. Additionally, LPS administration was accompanied by a significant increase in the number of macrophages, T helper (Th) 1 and Th17-related cytokines (P=0.009, P=0.008 and P=0.008, respectively). Therefore, the present model is commensurate with the characteristics of primary nasal polyps that have been identified in the Asian population.
研究已证实革兰氏阴性菌在难治性鼻息肉中起重要作用。在本研究中，使用脂多糖（LPS）建立嗜中性粒细胞性鼻息肉小鼠模型，以探讨LPS对小鼠嗜中性粒细胞性鼻息肉形成的影响及机制。将总共5或10μg的LPS滴入C57BL/6J小鼠的鼻腔，以建立嗜中性粒细胞性鼻息肉动物模型。采用组织学染色、Toll样受体4（TLR4）、巨噬细胞分化抗原68及嗜中性粒细胞髓过氧化物酶免疫组织化学法观察鼻黏膜的组织病理学变化。通过酶联免疫吸附测定法检测鼻腔灌洗液中细胞因子的表达水平，包括干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-4和IL-17。与对照组相比，LPS组小鼠出现明显的黏膜上皮细胞损伤和鼻息肉形成。此外，还发现TLR4细胞、巨噬细胞、嗜中性粒细胞以及鼻腔灌洗液中IFN-γ、TNF-α和IL-17水平显著升高（均P=0.008）。这些结果表明，LPS能够激活TLR4受体途径，诱导小鼠嗜中性粒细胞性鼻息肉的形成。此外，给予LPS后巨噬细胞数量以及T辅助（Th）1和Th17相关细胞因子显著增加（分别为P=0.009、P=0.008和P=0.008）。因此，本模型与在亚洲人群中已确定的原发性鼻息肉特征相符。
