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实验诱导兔鼻窦嗜酸性息肉。

Experimentally induced eosinophilic polyps in rabbit sinuses.

机构信息

Department of Otorhinolaryngology–Head and Neck Surgery, Jichi Medical University School of Medicine, Tochigi, Japan.

出版信息

Am J Rhinol Allergy. 2010 Sep-Oct;24(5):341-7. doi: 10.2500/ajra.2010.24.3519.

Abstract

BACKGROUND

Nasal polyps are one of the most common findings of physical examination in the otolaryngology area and the experimental model of nasal polyps in the rabbit maxillary sinus is helpful for clarifying the mechanism of polyp formation. Several protocols have been reported for this model, but most of them involved infectious polyps without eosinophil infiltration. We have attempted to establish a novel rabbit model of polyps associated with eosinophil infiltration.

METHODS

Rabbits were either untreated (group A) or sensitized with ovalbumin (OVA; groups B-D). After repeated exposure to OVA, some animals further received valine-glycine-serine-glutamine (group C) or poly-L-arginine (group D) in their maxillary sinuses for 4 weeks. Subsequently, sinus tissues were dissected and subjected to histological analysis. The changes in mRNA expression were analyzed by DNA microarray.

RESULTS

Remarkable histological changes were observed in groups C and D but not in group B in eosinophil number in the maxillary sinus mucosa, the width of the lamina propria, and polyp scoring. These changes in group D were greater than those in group C. DNA microarray analysis revealed that up-regulated genes in group D included those related to inflammation and extracellular matrix metabolism. On the other hand, down-regulated genes in group D involved those related to anti-inflammation.

CONCLUSION

Our results indicate that treatment with inflammatory agents, in combination with an antigen-dependent immune response, could induce nasal polyp formation associated with eosinophil infiltration and mucosal hypertrophy. The gene expression profile supported the clinical relevance of this model.

摘要

背景

鼻息肉是耳鼻喉科检查中最常见的发现之一,兔上颌窦鼻息肉实验模型有助于阐明息肉形成的机制。已经报道了几种该模型的方案,但大多数涉及无嗜酸性粒细胞浸润的感染性息肉。我们试图建立一种与嗜酸性粒细胞浸润相关的新型兔息肉模型。

方法

兔子未处理(A 组)或用卵清蛋白(OVA;B-D 组)致敏。反复暴露于 OVA 后,一些动物在其上颌窦中进一步接受缬氨酸-甘氨酸-丝氨酸-谷氨酰胺(C 组)或多聚精氨酸(D 组)4 周。随后,解剖窦组织并进行组织学分析。通过 DNA 微阵列分析 mRNA 表达的变化。

结果

在 C 组和 D 组中观察到显著的组织学变化,但在 B 组中未观察到上颌窦黏膜中的嗜酸性粒细胞数量、固有层宽度和息肉评分的变化。D 组的这些变化大于 C 组。DNA 微阵列分析显示,D 组上调的基因包括与炎症和细胞外基质代谢相关的基因。另一方面,D 组下调的基因涉及与抗炎相关的基因。

结论

我们的结果表明,用炎症剂治疗,结合抗原依赖性免疫反应,可诱导与嗜酸性粒细胞浸润和黏膜肥大相关的鼻息肉形成。基因表达谱支持该模型的临床相关性。

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