{"title":"Development and validation of a Guinea pig model for concurrent allergic rhinitis and asthma using recombinant Der f 2.","authors":"Feng Xu, Li Hu, Jianzhong Wang, Lineng Zhang","doi":"10.1186/s12890-025-03534-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop a guinea pig model of concurrent allergic rhinitis and asthma.</p><p><strong>Methods: </strong>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)<sub>3</sub> 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)<sub>3</sub> 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)<sub>3</sub> 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9148,"journal":{"name":"BMC Pulmonary Medicine","volume":"25 1","pages":"79"},"PeriodicalIF":2.6000,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829409/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Pulmonary Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12890-025-03534-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
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)3 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)3 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)3 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.
背景:本研究旨在建立过敏性鼻炎并发哮喘的豚鼠模型。方法:将33只豚鼠随机分为对照组和试验组。实验组豚鼠于第1天和第8天腹腔注射重组野生型farinophaides farinae 2组过敏原(wt Der f2) + Al(OH)3致敏,第16天和第23天吸入wt Der f2气溶胶致敏。致敏豚鼠于第19天和第26天鼻内注射wt Der 2加Al(OH)3凝胶进行鼻腔症状评分,并于第30天进行活动性皮肤过敏反应(ACA)试验。对照组豚鼠平行给予生理盐水(N.S.)加氢氧化铝(OH)3。进行皮肤刺激试验以排除非过敏豚鼠,并进行鼻腔症状评估以排除非过敏豚鼠。最后通过ACA试验、wt Der f2 Evans蓝染色定量、组织病理学评价、鼻黏膜和肺组织MUC5AC表达的免疫组化分析对过敏性气道模型进行验证。结果:皮肤反应阴性的豚鼠2只,鼻症状评分低于5分的豚鼠3只被排除出实验组。ACA试验显示实验组过敏反应增强,体外渗出的Evans蓝染料定量显示wt Der f2斑点的吸光度明显高于mu Der f2。组织学分析显示过敏性鼻炎和哮喘的典型病理特征。实验组鼻黏膜和肺标本中MUC5AC水平显著高于对照组。结论:采用致敏、激发和验证相结合的方法,我们成功建立了一种适合病理生理学研究的变应性鼻炎和哮喘并发豚鼠模型。临床试验号:不适用。
期刊介绍:
BMC Pulmonary Medicine is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of pulmonary and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.