布地奈德对变应性鼻炎嗅觉障碍干预作用的实验研究

Experimental Research of the Intervention Effects of Budesonide on Olfactory Dysfunction by Allergic Rhinitis

目的观察变应性鼻炎(AR)对嗅觉功能的影响及布地奈德对AR嗅觉障碍的干预效果。方法应用卵清蛋白致敏并激发BALB/C小鼠,建立AR小鼠模型。应用埋藏小球实验(BFT)评估AR小鼠嗅觉功能。HE染色及免疫组化法观察AR小鼠嗅黏膜的组织形态学变化及嗅觉标记蛋白(OMP)表达的变化。鼻内滴用布地奈德对AR小鼠进行干预,分别在开始干预后第7天及第14天应用免疫组化方法检测小鼠嗅黏膜OMP表达的变化。结果对成功建模的AR小鼠进行嗅觉功能评估,42/55的AR小鼠在AR的基础上伴有嗅觉障碍。与对照组相比较,AR小鼠嗅黏膜的上皮层明显变薄,嗅感受神经元(ORNs)的层数减少,排列紊乱。AR小鼠嗅黏膜OMP表达较对照组减少。与不用药组相比较,布地奈德干预1组的小鼠嗅黏膜OMP表达增加,嗅上皮OMP染色阳性细胞数量增多,差异有统计学意义(P<0.05)。接近对照组OMP染色阳性细胞数量,与对照组相比较差异无统计学意义(P>0.05)。布地奈德干预2组OMP表达与布地奈德干预1组相似,差异无统计学意义(P>0.05)。结论在本实验中,AR小鼠嗅黏膜上皮层变薄,ORNs层数减少,OMP表达减低,证明了AR引起嗅觉障碍的作用机制除鼻腔气道阻塞的原因外,嗅黏膜本身因炎症发生的变化也是重要的原因。糖皮质激素是临床治疗嗅觉障碍的常用药物,本实验对伴有嗅觉障碍的AR小鼠鼻内滴用布地奈德进行干预,观察到嗅上皮OMP表达明显增加,ORNs的数量增多,且干预效果可在停药后维持一段时间。因此,鼻内局部应用糖皮质激素可以对嗅黏膜产生影响,是治疗AR引发的嗅觉障碍的有效方法。

Objective To observe the influence of allergic rhinitis（AR） over olfactory function and the intervention effects of Budesonide on olfactory dysfunction.Methods An allergic rhinitis mini mouse model was established by intraperi toneal injection and intranasal application of ovalubumin to mice.The olfactory function of the mice was evaluated by buried food test（BFT）.HE dyeing and immunohistochemistry were used to observe the tissues morphology change of olfactory mucosa in AR mini mice and OMP expression.The AR mini mice were intervened through intranasal application of budesonide and the change of OMP expression was detected by immunohistochemistry 7 and 14 days after intervention respectively.Results The olfactory function evaluation of AR mini mice model indicated that the incidence rate of olfactory dysfunction in allergic rhinitis mice was 76.36%.The olfactory epithelium became thinner and layer numbers of ORNs were decreased with disorder arrangement in AR mice than those in control group.OMP expression in AR mini mice was decreased than that in control group.Compared with other drug groups,the olfactory OMP expression in Budesonide intervention group 1 was increased,the number of OMP dyeing positive cells in olfactory epithelium was increased,and the difference was significant（P0.05）.There was no significant difference in numbers of the OMP dyeing positive cells which were similar to that in control group between Budesonide group 1 and the control group（P0.05）.While the expression of OMP in budesonide group 2 was similar to that in Budesonide group 1 and the difference in the numbers of OMP dyeing positive cells was not significant（P0.05）.Conclusion In this study,the olfactory epithelium becomes thinner in AR mice,layer numbers of ORNs were decreased and the expression of OMP in olfactory epithelium is down-regulated,which proved that the mechanism of olfactory dysfunction due to allergic rhinitis is not only the blockage of nasal cavity but also the change of mucosa by inflammation.Glucocorticoids are the common used drugs in treating olfactory dysfunction,after intranasal application of glucocorticoid,the significant up-regulate of OMP in olfactory mucosa in mice and the rise of ORNs layers were observed and such intervention effect can keep for a while after drug withdrawl.So it can be proved that the intranasal application of budesonide can have an effect on olfactory mucosa and is a sure method in treating with olfactory dysfunction in allergic rhinitis.