符合变应性鼻炎临床客观特征的大鼠模型初步建立
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摘要
目的建立符合临床客观特征的变应性鼻炎大鼠模型。方法 21只Wistar大鼠,随机分为模型组(9只)和对照组(9只),另有3只大鼠用于被动皮肤过敏(PCA)实验。模型组以卵清蛋白作为变应原,完成基础致敏;继以2%卵清蛋白生理盐水进行鼻内激发。对照组以生理盐水替代卵清蛋白。采用PCA实验、行为学评分、Luna染色、HE染色对所建模型进行综合评价。结果模型组基础致敏阶段完成后,PCA实验阳性,证明变应原特异性免疫球蛋白E产生;鼻内激发阶段完成后,每只大鼠行为学评分均>5分,出现喷嚏、鼻痒、流清涕等典型症状;Luna染色示鼻中隔黏膜下嗜酸性粒细胞增多、浸润;HE染色示鼻黏膜嗜酸性粒细胞浸润,杯状细胞增多,部分黏膜上皮脱落。对照组无上述变化。结论初步建立产生变应原特异性免疫球蛋白E和嗜酸性粒细胞升高的符合变应性鼻炎发作时临床特征的变应性鼻炎大鼠模型。
Objective To establish a rat model of allergic rhinitis(AR) which is consistent with the clinical objective features.Methods 21 Wistar rats were randomly divided into model group(n=9) and control group(n=9),and another 3 normal rats were used for passive cutaneous anaphylaxis(PCA).The model group used ovalbumin(OVA) as an allergen to complet basic sensitization;followed by 5% OVA saline nasal challenge.The control group used normal saline instead of OVA.By the PCA test,the behavioral score,Luna staining,HE staining,the model was comprehensively evaluated.Results For the model group,PCA(+) proved the production of allergen specific Ig E after the completion of the basic sensitization phase;each rat behavioral score was greater than 5,appearing the typical symptoms such as sneezing,nasal itching,rhinorrhea after the completion of nasal challenge;Luna staining showed the nasal septum mucosa eosinophilia infiltration;HE staining showed the nasal mucosal eosinophilia,goblet cells increased,part of epithelial shedding.The control group had no such changes.Conclusion This study has successfully established the AR rat model which had the characteristics of the two differential diagnosis:the production of allergen specific Ig E and eosinophilia and was in accordance with the onset of clinical symptoms of human AR.
Objective To establish a rat model of allergic rhinitis(AR) which is consistent with the clinical objective features.Methods 21 Wistar rats were randomly divided into model group(n=9) and control group(n=9),and another 3 normal rats were used for passive cutaneous anaphylaxis(PCA).The model group used ovalbumin(OVA) as an allergen to complet basic sensitization;followed by 5% OVA saline nasal challenge.The control group used normal saline instead of OVA.By the PCA test,the behavioral score,Luna staining,HE staining,the model was comprehensively evaluated.Results For the model group,PCA(+) proved the production of allergen specific Ig E after the completion of the basic sensitization phase;each rat behavioral score was greater than 5,appearing the typical symptoms such as sneezing,nasal itching,rhinorrhea after the completion of nasal challenge;Luna staining showed the nasal septum mucosa eosinophilia infiltration;HE staining showed the nasal mucosal eosinophilia,goblet cells increased,part of epithelial shedding.The control group had no such changes.Conclusion This study has successfully established the AR rat model which had the characteristics of the two differential diagnosis:the production of allergen specific Ig E and eosinophilia and was in accordance with the onset of clinical symptoms of human AR.
引文
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[3]王翠娟,李培杰,王晓琴,等.右美托咪定联合亚低温对脓毒症大鼠炎症反应的影响[J].兰州大学学报:医学版,2016,42(6):25—30
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[8]蔺林,严文洪,赵霞.氢氧化铝佐剂对变应性鼻炎小鼠模型的影响[J].临床耳鼻咽喉头颈外科杂志,2014,28(11):780—784
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[11]Mota I.Passive cutaneous anaphylaxis induced with mast cell sensitizing antibody:the role of histamine and 5-hydroxytryptamine[J].Life Sciences,1963,12(12):917—927
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[13]江英,席克虎,陈小婉,等.18β-甘草次酸对变应性鼻炎大鼠鼻黏膜纤毛超微结构的影响[J].第二军医大学学报,2015,36(1):26—33
[14]胡艳菲,唐方.过敏性鼻炎动物模型研究进展[J].医学研究生学报,2012,25(5):540—543
[15]Sehmi R,Wood LJ,Watson R,et al.Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+cells from asthmatic subjects:a novel marker of progenitor cell commitment towards eosinophilic differentiation[J].J Clin Invest,1997,100(10):2466—2475
[16]李萌,魏肖云,戴启刚,等.变应性鼻炎动物模型的研究现状[J].现代中西医结合杂志,2013,22(12):1360—1363
[17]何金年,谭建成,姚东方,等.鼻内类固醇激素对变应性鼻炎动物模型鼻腔黏膜的影响[J].临床耳鼻咽喉头颈外科杂志,2012,26(2):74—77
[18]中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组,中华医学会耳鼻咽喉头颈外科分会鼻科学组.变应性鼻炎诊断和治疗指南(2015年,天津)[J].中华耳鼻咽喉头颈外科杂志,2016,51(1):6—19
[19]Okubo K,Kurono Y,Fujieda S,et al.Japanese guideline for allergic rhinitis[J].Allergology International,2011,60(2):171—189
[20]Skoner DP.Allergic rhinitis:definition,epidemiology,detection,and pathophysiology,diagnosis[J].J Allergy Clin Immunol,2001,108(Suppl 1):2—8
[21]Naclerio RM.Allergic rhinitis[J].N Engl J Med,1991,325(12):860—869
[22]马毅,桂岩,王有虎,等.18β-甘草次酸对变应性鼻炎大鼠鼻黏膜上皮细胞紧密连接的影响[J].临床耳鼻咽喉头颈外科杂志,2014,28(20):1590—1594
[23]李娟丽,席克虎,侯赟,等.18β-甘草次酸对变应性鼻炎大鼠鼻黏膜中CCL11、AQP1和EOS表达的影响[J].四川大学学报:医学版,2015,46(3):389—393
[24]梁宗星,郭琳,梁峰,等.大鼠被动皮肤过敏试验方法研究[J].毒理学杂志,2012,26(3):195—197
[25]Broide DH.Allergic rhinitis:pathophysiology[J].Allergy Asthma Proc,2010,31(5):370—374
[2]Bousquet J,Schunemann HJ,Samolinski B,et al.Allergic rhinitis and its impact on asthma(ARIA):achievements in 10 years and future needs[J].J Allergy Clin Immunol,2012,130(5):1049—1062
[3]王翠娟,李培杰,王晓琴,等.右美托咪定联合亚低温对脓毒症大鼠炎症反应的影响[J].兰州大学学报:医学版,2016,42(6):25—30
[4]锡琳,张罗,张伟.变应性鼻炎动物模型若干问题[J].国际耳鼻咽喉头颈外科杂志,2008,32(2):81—84
[5]Greiner AN,Hellings PW,Rotiroti G,et al.Allergic rhinitis[J].Lancet,2011,378(9809):2112—2122
[6]Peterson1 TS,Spitsbergen JM,Feist SW,et al.Luna stain,an improved selective stain for detection of microsporidian spores in histologic sections[J].Dis Aquat Organ,2011,95(2):175—180
[7]Jung JH,Kang IG,Kim DY,et al.The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis[J].J Ginseng Res,2013,37(2):167—175
[8]蔺林,严文洪,赵霞.氢氧化铝佐剂对变应性鼻炎小鼠模型的影响[J].临床耳鼻咽喉头颈外科杂志,2014,28(11):780—784
[9]胡华.P物质小干扰RNA在变应性鼻炎基因治疗中的作用机制研究[D].上海:复旦大学,2011
[10]赵宇,C.Andrew van Hasselt,吴港生,等.卵白蛋白经鼻致敏建立变应性鼻炎动物模型[J].中华耳鼻咽喉头颈外科杂志,2005,40(3):175—180
[11]Mota I.Passive cutaneous anaphylaxis induced with mast cell sensitizing antibody:the role of histamine and 5-hydroxytryptamine[J].Life Sciences,1963,12(12):917—927
[12]赵秀杰,董震,杨占泉,等.鼻超敏反应实验模型的建立[J].中华耳鼻咽喉科杂志,1993,28(1):17—18
[13]江英,席克虎,陈小婉,等.18β-甘草次酸对变应性鼻炎大鼠鼻黏膜纤毛超微结构的影响[J].第二军医大学学报,2015,36(1):26—33
[14]胡艳菲,唐方.过敏性鼻炎动物模型研究进展[J].医学研究生学报,2012,25(5):540—543
[15]Sehmi R,Wood LJ,Watson R,et al.Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+cells from asthmatic subjects:a novel marker of progenitor cell commitment towards eosinophilic differentiation[J].J Clin Invest,1997,100(10):2466—2475
[16]李萌,魏肖云,戴启刚,等.变应性鼻炎动物模型的研究现状[J].现代中西医结合杂志,2013,22(12):1360—1363
[17]何金年,谭建成,姚东方,等.鼻内类固醇激素对变应性鼻炎动物模型鼻腔黏膜的影响[J].临床耳鼻咽喉头颈外科杂志,2012,26(2):74—77
[18]中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组,中华医学会耳鼻咽喉头颈外科分会鼻科学组.变应性鼻炎诊断和治疗指南(2015年,天津)[J].中华耳鼻咽喉头颈外科杂志,2016,51(1):6—19
[19]Okubo K,Kurono Y,Fujieda S,et al.Japanese guideline for allergic rhinitis[J].Allergology International,2011,60(2):171—189
[20]Skoner DP.Allergic rhinitis:definition,epidemiology,detection,and pathophysiology,diagnosis[J].J Allergy Clin Immunol,2001,108(Suppl 1):2—8
[21]Naclerio RM.Allergic rhinitis[J].N Engl J Med,1991,325(12):860—869
[22]马毅,桂岩,王有虎,等.18β-甘草次酸对变应性鼻炎大鼠鼻黏膜上皮细胞紧密连接的影响[J].临床耳鼻咽喉头颈外科杂志,2014,28(20):1590—1594
[23]李娟丽,席克虎,侯赟,等.18β-甘草次酸对变应性鼻炎大鼠鼻黏膜中CCL11、AQP1和EOS表达的影响[J].四川大学学报:医学版,2015,46(3):389—393
[24]梁宗星,郭琳,梁峰,等.大鼠被动皮肤过敏试验方法研究[J].毒理学杂志,2012,26(3):195—197
[25]Broide DH.Allergic rhinitis:pathophysiology[J].Allergy Asthma Proc,2010,31(5):370—374