清醒挪威褐鼠过敏性哮喘发作全程记录模型  

Evaluation of asthma exacerbation in an ovalbumin-sensitized conscious Brown Norway rat model

作　　者：陶婧婧[1] 徐燕锋[1] 韩云林[1] 徐玉环[1] 秦川[1] 高虹[1] 张星东[1] 

机构地区：[1]卫生部人类疾病比较医学重点实验室国家中医药管理局人类疾病动物模型三级实验室中国医学科学院医学实验动物研究所北京协和医学院比较医学中心,北京100021

出　　处：《中国比较医学杂志》2015年第6期1-8,82,共9页Chinese Journal of Comparative Medicine

基　　金：中国医学科学院医学实验动物研究所人才引进基金(编号:DWS201202);973计划(2011CB504903);863计划(2013AA020106)

摘　　要：目的建立卵蛋白(OVA)致敏激发后,在挪威褐鼠无创且清醒的状态下,可观察和记录到过敏性哮喘发作全过程(速发相和迟发相)的动物模型。方法 66只挪威褐鼠按致敏液[OVA和Al(OH)3]不同平均分为11组,单纯注射OVA的4组(0.01、0.1、1.0和10.0 mg/只);OVA混合Al(OH)3干粉的5组(0.1+100、1.0+100、10.0+100、1.0+52和1.0+4 mg/只);OVA混合Al(OH)3胶体的1组(10.0+4 mg/只);正常对照组1组。10个致敏组分别于第0天和第5天背部皮下2点注射相应致敏液,每点注射0.2 m L,正常对照组注射等量生理盐水。在第37天雾化吸入5%OVA激发10 min。然后立即放入体积描记器中连续记录16 h呼气相延长参数(penh)值。采集第0、7、14、21、28、35、38天血清,ELISA法检测特异性Ig E含量。HE染色观察肺病理变化。结果除单纯注射OVA 0.01 mg组外,其他各组大鼠血清特异性Ig E含量均比正常对照组显著升高(P<0.05),且在致敏1周后Ig E开始大量产生,直到第5周均呈持续增长趋势。观察到了哮喘发作的速发和迟发双相气道反应,其特点表现在Penh值的显著增高,且与正常对照组相比,模型组(以OVA 10.0&Al(OH)3100、OVA 10.0&Al(OH)3gel 4组为例)的速发相/迟发相峰值、面积均显著增大(P<0.05)。模型组(以OVA 10.0&Al(OH)3100组为例)有以气道周围嗜酸性粒细胞浸润为主的炎症表现。结论成功建立了无创、清醒状态下挪威褐鼠过敏性哮喘发作全程记录模型。Objective To establish an animal model in which both early-phase asthmatic response( EAR) and latephase asthmatic response( LAR) can be observed after sensitization and subsequent inhalation challenge with ovalbumin( OVA). Animals were conscious with no narcotic used,unrestricted,and fed ad libitum. Methods Sixty-six SPF6-8-week old male Brown Norway rats were divided into eleven equal groups. All groups of rats except normal control group were injected subcutaneously with 0. 4 m L( sc in back,2 sites,0. 2 m L / site) OVA or OVA + Al( OH)3solution on day 0and day 5. Four groups were given OVA only at the dose of 0. 01,0. 1,1. 0 or 10. 0 mg / rat,five groups were given OVA +Al( OH)3powder at the dose of 0. 1 + 100,1. 0 + 100,10. 0 + 100,1. 0 + 52 and 1. 0 + 4 mg / rat,one group was given OVA+ Al( OH)3gel at the dose of 10. 0 + 4 mg / rat. Normal control group was injected subcutaneously with the same volume of saline. All the groups were challenged for 10 minutes with 5 m L 5% OVA aerosol on day 37. Enhanced pause( Penh) was recorded for 16 hours in a whole-body plethysmography system after challenge. Specific Ig E of the serum samples on day 0,7,14,21,28,35,38 were measured by ELISA. Pulmonary pathological changes were observed using HE staining. Results Compared with the normal control group,immunized rats except the group given 0. 01 mg OVA produced specific Ig E( P <0. 05),and the content of Ig E grew sharply after 7 days,and always kept growing until 5 weeks. The whole course of asthma exacerbation was recorded successfully. The rats developed EAR and / or LAR within 16 hours following OVA challenge.Especially the groups injected with 10 mg OVA and 100 mg Al( OH)3or 4 mg Al( OH)3gel showed steady pattern of biphasic airway responses and their EAR or LAR peak,and the area under the curve were increased significantly compared with those of the normal control group( P < 0. 05). Inflammation characterized by eosinophil infiltration was observed in the rat lung of model group( OVA 10. 0 & Al( OH)3100 group as a re

关 键 词：过敏性哮喘 挪威褐鼠 呼气相延长参数 速发相反应 迟发相反应 

分 类 号：R562.25[医药卫生—呼吸系统] R[医药卫生—内科学]