细菌性和变应性慢性鼻窦炎小鼠的组织学和免疫学观察。

Heng Wang, Xiang Lu, Ping-Ping Cao, Yan Chu, Xiao-Bo Long, Xin-Hao Zhang, Xue-Jun You, Yong-Hua Cui, Zheng Liu
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引用次数: 36

摘要

背景:本研究旨在探讨细菌性慢性鼻窦炎(BCRS)和变应性慢性鼻窦炎(ACRS)小鼠模型的组织学和免疫学特征。方法:采用肺炎链球菌接种加美敦力公司Merocel (Medtronic, Jacksonville, FL)封堵12周建立BCRS小鼠模型。采用卵清蛋白(OVA)腹腔注射和连续12周的OVA鼻灌胃方法建立ACRS小鼠模型。采用苏木精和伊红染色观察两种模型鼻窦粘膜的组织学变化,对一般形态学和炎症细胞进行染色,对杯状细胞进行周期性酸-希夫染色,对胶原进行马松三色染色。采用酶联免疫吸附法检测鼻灌洗液中各种细胞因子的浓度。结果:BCRS模型固有层多形核中性粒细胞浸润更为明显,而ACRS模型嗜酸性粒细胞浸润更为明显。两种模型均可见明显的杯状细胞和上皮下腺增生、上皮下纤维化、上皮增厚、单核细胞浸润,其中ACRS模型更为严重。两种模型NLF的白细胞介素(IL)-6和肿瘤坏死因子α水平均升高,并在第1周达到峰值。干扰素γ水平在两种模型中均上调,但在BCRS模型第1周和ACRS模型第4周达到最大值。IL-8 (CXCL8)水平仅在BCRS小鼠中升高,并在1周达到峰值,而IL-5、IL-13和eotaxin (CCL11)水平仅在ACRS小鼠中升高,并在1周达到峰值。BCRS小鼠的Th1/Th2比值显著高于ACRS小鼠(6.68 +/- 2.33 vs 1.37 +/- 0.86;P < 0.01)。结论:BCRS和ACRS小鼠模型的组织学和免疫学特征分别与人非嗜酸性CRS和嗜酸性CRS相似。BCRS和ACRS小鼠模型具有不同的免疫特性,适用于CRS研究。
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Histological and immunological observations of bacterial and allergic chronic rhinosinusitis in the mouse.

Background: The purpose of this study was to elucidate histological and immunologic features of mouse models of bacterial chronic rhinosinusitis (BCRS) and allergic chronic rhinosinusitis (ACRS).

Methods: A BCRS mouse model was established using Streptococcus pneumoniae inoculation plus Merocel (Medtronic, Jacksonville, FL) ostiomeatal obstruction for 12 weeks. An ACRS mouse model was developed by means of ovalbumin (OVA) i.p. injection and subsequent repeated OVA intranasal challenge for 12 weeks. Histological changes of sinonasal mucosa of both models were examined by means of hematoxylin and eosin staining for general morphology and inflammatory cell, periodic acid-Schiff staining for goblet cell, and Masson-trichrome staining for collagen. Enzyme-linked immunosorbent assay was used to detect the concentrations of various cytokines in nasal lavage fluid.

Results: Polymorphonuclear neutrophil infiltration in lamina propria was more obvious in the BCRS model, whereas eosinophil infiltration was more apparent in the ACRS model. Significant goblet cell and subepithelial gland hyperplasia, subepithelial fibrosis, epithelial thickening, and mononuclear cell infiltration were shown in both models with more severe extent found in the ACRS model. Interleukin (IL)-6 and tumor necrosis factor alpha levels in NLF from both models were increased and peaked at 1 week. Interferon gamma levels were also up-regulated in both models but reached maximum at 1 week in the BCRS model and 4 weeks in the ACRS model. IL-8 (CXCL8) levels were only increased in BCRS mice and peaked at 1 week, whereas IL-5, IL-13, and eotaxin (CCL11) levels were only enhanced in ACRS mice and peaked at 1 week. The Th1/Th2 ratio in BCRS mice was significantly higher than that in ACRS mice (6.68 +/- 2.33 versus 1.37 +/- 0.86; p < 0.01).

Conclusion: Histological and immunologic features of BCRS and ACRS mouse models were similar to those of human noneosinophilic and eosinophilic CRS, respectively. BCRS and ACRS mouse models have distinct immunologic characteristics and are applicable for CRS research.

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