抗原长期刺激致变应性鼻炎豚鼠模型鼻黏膜重塑的研究  

Prolonged allergen challenge in a guinea pig model of allergic rhinitis leads to nasal mucosa remodeling

作　　者：江满杰[1] 李泽卿[1] 吴晋蓉[2] 周玫[1] 王天友[1] 张勇[1] 王志颐[1] 王秋萍[1] 

机构地区：[1]南京军区南京总医院耳鼻咽喉-头颈外科,南京210002 [2]南京军区南京总医院病理科

出　　处：《临床耳鼻咽喉头颈外科杂志》2012年第5期218-222,共5页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：江苏省基础研究计划面上项目(No:BK2006134)

摘　　要：目的:观察抗原长期刺激致变应性鼻炎豚鼠模型鼻黏膜重塑的特点。方法:Hartley豚鼠48只,随机分为6组(每组8只),即实验组用卵清蛋白(OVA)激发(OVA2W组、OVA6W组和OVA12W组),对照组用生理盐水激发(Sal2W组、Sal6W组和Sal12W组)。OVA制备变应性鼻炎动物模型,抗原刺激分别持续2W、6W和12W,在最后一次激发24h后行鼻腔灌洗、取鼻黏膜组织。ELISA法检测鼻腔灌洗液中OVA特异性免疫球蛋白(OVA-sIgE)、嗜酸粒细胞阳离子蛋白(ECP)含量;鼻黏膜组织切片采用苏木精-伊红、AB-PAS和MT法染色,计数鼻黏膜上皮杯状细胞数量,测量上皮细胞损伤程度、基膜胶原含量;免疫组织化学法检测鼻黏膜组织转移生长因子β1(TGF-β1)的表达。结果:①OVA6W、OVA12W组与OVA2W组比较,OVA-sIgE含量均差异有统计学意义(均P<0.05),而ECP含量在3个实验组中无明显差别;实验组与相应的对照组比较,OVA-sIgE、ECP含量均差异有统计学意义(均P<0.01)。②OVA6W、OVA12W组与OVA2W组比较,0级、1级上皮细胞损伤均差异有统计学意义(均P<0.01);实验组0级、1级上皮损伤与相应的对照组相比差异有统计学意义(均P<0.05)。③鼻黏膜杯状细胞增生和基膜胶原沉积,OVA6W、OVA12W组与OVA2W组比较均差异有统计学意义(均P<0.01);对照组杯状细胞数均较相应的实验组明显减少(均P<0.05);Sal6W、Sal12W组基膜胶原沉积均较相应的实验组明显减少(均P<0.05)。④OVA6W、OVA12W组与OVA2W组比较,TGF-β1的表达均差异有统计学意义(均P<0.01);实验组与相应的对照组比较,TGF-β1的表达均差异有统计学意义(均P<0.01)。结论:鼻黏膜上皮细胞损伤、杯状细胞增生和细胞外基质胶原沉积是变应性鼻炎鼻黏膜组织重塑的特点;在抗原激发早期,表现为上皮损伤,与重塑相关的细胞因子表达增强,随着抗原刺激延长,表现出腺体增生和胶原沉积的特征越明显。Objective：The aim of this study was to use a guinea pig model of prolonged allergic-induced rhinitis to characterize the feature of nasal mucosa remodeling.Method：Forty-eight male Hartley guinea pigs were randomly divided into six groups： allergen challenged groups（Group OVA2W,Group OVA6W and Group OVA12W） and control groups respectively（Group Sal2W,Group Sal6W and Group Sal12W）.Each group had 8 guinea pigs.To develop a guinea pig model of nasal mucosa remodeling,ovalbumin-sensitized guinea pigs were repeatedly challenged with allergen twice a week from two weeks to 12 weeks.Matched control groups were challenged with physiological saline.Nasal lavage was performed 24 hours after the last intranasal challenge.Then nasal mucosa were obtained.HE,AB-PAS,MT,and immunohistochemical staining against transforming growth factor-β1（TGF-β1） were performed.Eosinophil cationic protein（ECP） and OVA-special IgE（OVA-sIgE） were detected by ELISA in nasal lavage fluid.Result：①The levels of OVA-sIgE in nasal lavage fluid in Group OVA6W and Group OVA12W were significantly different from Group OVA2W,while the levels of ECP had no significant difference among the experiment groups.The levels of OVA-sIgE and ECP in experiment groups were significantly different from control groups respectively（P0.01）.②Grade 0 and Grade 1 of epithelial damage were significantly different in Group OVA6W and Group OVA12W when compared with from Group OVA2W（P0.01）.At the same time,Grade 0 and Grade 1 of epithelial damage were statistically different in the experiment groups when compared with the respectively control groups（P0.05）.③ Goblet gland hyperplasia and collagen deposit within the extracellular matrix（ECM） were easily found in Group OVA6W and Group OVA12W compared with Group OVA2W（P0.01）.The number of goblet gland and the ratio of collagen deposit were statistically more in Group OVA6W and Group OVA12W than in Group Sal6W and Group Sal12W（P0.05）.That feature of the ratio of collagen depos

关 键 词：鼻炎 变应性 鼻黏膜重塑 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]