鼻用激素剂量差异对变应性鼻炎小鼠鼻黏膜重塑及MMP-9表达的影响

连媛媛; 张念凯; 刘婷婷

doi:10.13201/j.issn.1001-1781.2015.05.019

鼻用激素剂量差异对变应性鼻炎小鼠鼻黏膜重塑及MMP-9表达的影响

- 青岛大学附属医院耳鼻咽喉头颈外科(青岛, 266000)
基金项目:
山东省科技发展计划(政策引导类):鼻用皮质类固醇激素剂量对变应性鼻炎大鼠鼻黏膜影响的实验研究(No:2011YD18022)

详细信息

通讯作者: 张念凯,E-mail:znkent@163.com

中图分类号: R765.21

收稿日期: 2014-12-27

Different intranasal corticosteroids effects on nasal airway remodeling of allergic rhinitis murine and matrix metalloproteinase-9

- Department of Otorhinolaryngology-Head and Neck Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266000, China

More Information

Corresponding author: ZHANG Niankai, E-mail: znkent@163.com

Received Date: 27 December 2014

摘要

摘要: 目的: 探讨不同剂量鼻用激素对变应性鼻炎(AR)小鼠鼻黏膜重塑及基质金属蛋白酶-9(MMP-9)表达的影响。方法: 将30只雌性BALB/c小鼠随机分为5组,A组[生理盐水组(NS组)], B组[卵清蛋白组(OVA组)],D1组(低剂量布地奈德组),D2组(中剂量布地奈德组)及D3组(高剂量布地奈德组)。分别接受OVA或NS腹腔注射、鼻部激发。D1、D2及D3组小鼠使用不同剂量的布地奈德鼻喷激素(0.6 μg/20 g、3.0 μg/20 g、15.0 μg/20 g)喷鼻12周,1次/d。分别在4周末及16周末评估小鼠鼻部症状学的变化,并于16周末取小鼠鼻腔组织分别行苏木精-伊红染色、PAS及MT法染色评估其鼻腔黏膜重塑变化。使用ELISA测定小鼠鼻腔黏膜MMP-9的含量。结果: 16周末B组小鼠的挠鼻、喷嚏次数及嗜酸粒细胞浸润个数均较A组增多,且出现杯状细胞增多,黏膜下腺体增生、肥大,上皮下纤维化及胶原沉积的变化。0.6 μg/20 g的布地奈德治疗可以抑制AR小鼠的鼻部症状学变化及嗜酸粒细胞浸润,而对于鼻腔黏膜重塑变化则需要至少3.0 μg/20 g的鼻喷激素。鼻喷激素可以抑制AR小鼠鼻腔中MMP-9的分泌。结论: 高剂量鼻用激素可能通过抑制AR小鼠鼻腔MMP-9的分泌,抑制鼻腔黏膜重塑的发展。
- 黏膜重塑 /
- 鼻炎 /
- 变应性 /
- 小鼠 /
- 布地奈德 /
- 基质金属蛋白酶-9
Abstract: Objective: To discuss the effect of different doses intranasal corticosteroids on remodeling of allergic rhinitis (AR) mice nasal mucosa and expression level of matrix metalloproteinase-9 (MMP-9).Method: Thirty BALB/c female mice were divided into five groups randomly and received OVA or normal saline(NS) with intraperitoneal injection or nasal challenge, respectively. The treatment groups received additional different doses of budesonide (0.6 μg/20 g, 3.0 μg/20 g and 15.0 μg/20 g) daily for 16 weeks. We assessed the nasal symptoms at 4 and 16 weeks. Collected the mice nasal tissue, and then stained with hematoxylin-eosin, Masson's Trichrome, and periodic acid-schiff respectively to evaluate airway remodeling at 16 weeks. MMP-9 was measured with enzyme-linked immunosorbent assay (ELISA).Result: Times of rubbing, sneezes and infiltrate of eosinophil increased more in B group than in A group, and subepithelial fibrosis, collagen deposition, goblet cell hyperplasia, and submucosal gland hypertrophy were only observed in B group at 16 weeks. The nasal symptoms and eosinophil infiltration were inhibited by treatment with budesonide from a dose of 0.6 μg onwards, while the prevention of structure changes was only observed with 3.0 μg onwards. In addition, intranasal budesonide reduced MMP-9 in the nasal of AR mice.Conclusion: The study suggests that higher dose intranasal corticosteroids might inhibit the airway remodeling of nasal mucosa by reducing MMP-9.
- nasal mucosal remodeling /
- rhinitis /
- allergic /
- budesonide /
- matrix metalloproteinase-9 /

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