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使用重组Der f 2建立并发变应性鼻炎和哮喘豚鼠模型及其验证

Development and validation of a Guinea pig model for concurrent allergic rhinitis and asthma using recombinant Der f 2.

作者信息

Xu Feng, Hu Li, Wang Jianzhong, Zhang Lineng

机构信息

Department of Otolaryngology-Head and Neck Surgery, Zhongshan Hospital of Fudan University, Shanghai, P. R. China.

Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital of Fudan University, Shanghai, P. R. China.

出版信息

BMC Pulm Med. 2025 Feb 14;25(1):79. doi: 10.1186/s12890-025-03534-y.

DOI:10.1186/s12890-025-03534-y
PMID:39953469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11829409/
Abstract

BACKGROUND

This study aimed to develop a guinea pig model of concurrent allergic rhinitis and asthma.

METHODS

Thirty-three guinea pigs were randomly divided into the control group and the experimental group. Guinea pigs in the experimental group were sensitized by intraperitoneal injection of recombinant wild-type Dermatophagoides farinae group 2 allergen (wt Der f 2) plus Al(OH) on day 1 and 8, followed by inhalation of an aerosol of wt Der f 2 on day 16 and 23. The sensitized guinea pigs were challenged with intranasal instillation of wt Der f 2 plus Al(OH) gel on day 19 and 26 for nasal symptoms scoring, and on day 30 for the active cutaneous anaphylaxis (ACA) test. Control group guinea pigs received normal saline (N.S.) plus Al(OH) in parallel. Cutaneous provocation tests were performed to exclude nonsensitized guinea pigs, and nasal symptom assessments were conducted to exclude non-allergic guinea pigs from the study. The allergic airway model was finally validated using the ACA test, Evans blue dye quantification with wt Der f2, histopathology evaluation, and immunohistochemistry analysis of MUC5AC expression in both nasal mucosa and lung tissue.

RESULTS

Two guinea pigs with negative cutaneous reactions and three with less than 5 points of the nasal symptom assessment were excluded from the experimental group. The ACA test showed enhanced allergic reactions in the experimental group, and the quantification of extravasated Evans blue dye demonstrated significantly higher absorbance in the wt Der f 2 spots compared to mu Der f 2. Histologic analyses illustrated pathologic features typical of allergic rhinitis and asthma. MUC5AC levels in the nasal mucosa and lung samples were significantly higher in the experimental group than in the control group.

CONCLUSION

We successfully established a guinea pig model of concurrent allergic rhinitis and asthma using a combination of sensitization, challenge, and validation methodologies with the allergen Der f 2, suitable for pathophysiological studies.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景

本研究旨在建立一种变应性鼻炎和哮喘并发的豚鼠模型。

方法

33只豚鼠随机分为对照组和实验组。实验组豚鼠于第1天和第8天腹腔注射重组野生型粉尘螨第2组变应原(wt Der f 2)加氢氧化铝(Al(OH))致敏,随后于第16天和第23天吸入wt Der f 2气雾剂。致敏豚鼠于第19天和第26天经鼻滴入wt Der f 2加Al(OH)凝胶以进行鼻症状评分,并于第30天进行主动皮肤过敏反应(ACA)试验。对照组豚鼠同时给予生理盐水(N.S.)加Al(OH)。进行皮肤激发试验以排除未致敏的豚鼠,并进行鼻症状评估以排除非变应性豚鼠。最终通过ACA试验、wt Der f2的伊文思蓝染料定量、组织病理学评估以及鼻黏膜和肺组织中MUC5AC表达的免疫组织化学分析对变应性气道模型进行验证。

结果

实验组中2只皮肤反应阴性的豚鼠和3只鼻症状评估得分低于5分的豚鼠被排除。ACA试验显示实验组过敏反应增强,与mu Der f 2相比,wt Der f 2部位渗出的伊文思蓝染料定量显示吸光度显著更高。组织学分析显示了变应性鼻炎和哮喘的典型病理特征。实验组鼻黏膜和肺样本中的MUC5AC水平显著高于对照组。

结论

我们通过变应原Der f 2的致敏、激发和验证方法成功建立了一种变应性鼻炎和哮喘并发的豚鼠模型,适用于病理生理学研究。

临床试验编号

不适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/4eda5c6ad036/12890_2025_3534_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/62613f2d9deb/12890_2025_3534_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/3cf71ebf3cf4/12890_2025_3534_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/581fe5bf3f49/12890_2025_3534_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/fc67ff7b43f4/12890_2025_3534_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/06d92bc126d1/12890_2025_3534_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/4eda5c6ad036/12890_2025_3534_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/62613f2d9deb/12890_2025_3534_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/3cf71ebf3cf4/12890_2025_3534_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/581fe5bf3f49/12890_2025_3534_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/fc67ff7b43f4/12890_2025_3534_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/06d92bc126d1/12890_2025_3534_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d46/11829409/4eda5c6ad036/12890_2025_3534_Fig6_HTML.jpg

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