变应性鼻炎对嗅觉的影响及糖皮质激素干预作用的实验研究

发布时间：2018-04-13 19:30

本文选题：嗅觉 + 糖皮质激素　；参考：《北京协和医学院》2011年博士论文

【摘要】：目的 1.观察变应性鼻炎(AR)对嗅觉功能的影响。 2.观察变应性鼻炎对嗅粘膜组织形态学的影响及对嗅粘膜中嗅觉标记蛋白(OMP)表达的影响。 3.观察应用糖皮质激素干预变应性鼻炎对嗅粘膜中OMP表达的影响。 4.观察两种不同给药途径下干预效果的区别,探讨最佳给药途径。方法 1.应用卵清蛋白致敏并激发BALB/C小鼠,建立变应性鼻炎小鼠模型。 2.应用埋藏小球实验(BFT)评估变应性鼻炎小鼠嗅觉功能。 3.HE染色及免疫组化方法观察变应性鼻炎小鼠嗅粘膜的组织形态学变化及OMP表达的变化。 4.鼻内滴用布地奈德和腹腔内注射复方倍他米松。免疫组化方法检测应用糖皮质激素进行干预后7天及14天小鼠嗅粘膜OMP表达的变化。结果 1.对成功建模的AR小鼠进行嗅觉功能评估,75.3%的AR小鼠在变应性鼻炎的基础上伴有嗅觉障碍。 2.与对照组相比较,变应性鼻炎小鼠嗅粘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。变应性鼻炎小鼠嗅粘膜OMP表达较对照组减少。其中变应性鼻炎不伴嗅觉障碍组嗅上皮OMP染色阳性细胞数量较对照组减少,差异没有显著性(P0.05)；变应性鼻炎伴嗅觉障碍组嗅上皮OMP染色阳性细胞较对照组减少,差异有显著性(P0.05)。 3.药物干预后第7天,与不用药组相比较,布地奈德干预1组及复方倍他米松干预1组的小鼠嗅粘膜OMP表达增加,嗅上皮OMP染色阳性细胞数量增多,差异有显著性(P0.05)。接近对照组OMP染色阳性细胞数量,与对照组相比较差异没有显著性(P0.05)。 4.药物干预后第14天,布地奈德干预2组OMP表达与布地奈德干预1组相似,复方倍他米松干预2组OMP表达与复方倍他米松干预1组相似。布地奈德干预2组与复方倍他米松干预2组之间比较,OMP染色阳性细胞数量没有显著性差异(P0.05)。结论 1.在变应性鼻炎小鼠模型中,有75.3%的小鼠伴有嗅觉障碍。嗅觉障碍是AR的常见症状。 2.变应性鼻炎使小鼠嗅粘膜发生组织形态学变化,嗅上皮层变薄,嗅感受神经元(ORNs)层数减少。变应性鼻炎能够减低小鼠嗅粘膜中OMP的表达,减少ORNs的数量。 3.两种给药途径的糖皮质激素干预均能够增加变应性鼻炎小鼠嗅粘膜OMP的表达,增加ORNs的数量。且治疗效果均可在停药后维持一段时间。两者作用效果相似,可首选鼻内局部用糖皮质激素作为给药途径。小结糖皮质激素是临床治疗嗅觉障碍的常用药物,但作用机制尚不完全清楚。变应性鼻炎是引起嗅觉障碍的重要因素,其作用机制除鼻腔气道阻塞的原因外,嗅粘膜本身因炎症发生的变化也是重要的原因。本实验对变应性鼻炎小鼠的嗅粘膜进行了组织形态学的观察,并选择OMP作为研究指标,观察嗅上皮OMP表达的变化,探讨变应性鼻炎对嗅粘膜产生的影响。通过全身和局部两种给药途径对变应性鼻炎小鼠进行糖皮质激素干预后,探讨糖皮质激素对变应性鼻炎小鼠嗅粘膜OMP表达的影响。以期进一步探讨糖皮质激素治疗变应性鼻炎嗅觉障碍的可能机制和对嗅粘膜的保护作用,选择安全有效的给药途径。
[Abstract]:Purpose

1 . To observe the effect of allergic rhinitis ( AR ) on olfactory function .

2 . Observe the effect of allergic rhinitis on the morphology of olfactory mucosa and the expression of olfactory marker protein ( OMP ) in the olfactory mucosa .

3 . To observe the effect of glucocorticoid on OMP expression in olfactory mucosa .

4 . To observe the difference of intervention effect in two different routes of administration and to explore the optimal route of administration .

method

1 . The BALB / C mice were sensitized with egg albumin and BALB / C mice were excited , and the model of allergic rhinitis was established .

2 . BFT was used to evaluate the olfactory function of allergic rhinitis mice .

3.HE staining and immunohistochemistry were used to observe the morphological changes and OMP expression in the olfactory mucosa of allergic rhinitis mice .

4 . The expression of OMP in the olfactory mucosa of mice 7 and 14 days after intervention with glucocorticoid was detected by immunohistochemistry .

Results

1 . To evaluate the olfactory function of AR mice successfully modeled , 75.3 % of AR mice were associated with olfactory dysfunction on the basis of allergic rhinitis .

2 . Compared with the control group , the epithelial layer of olfactory mucosa of allergic rhinitis mice was significantly thinner , the number of olfactory sensory neurons ( ORNs ) decreased and the arrangement was disturbed . The expression of OMP in olfactory mucosa of allergic rhinitis mice was lower than that in the control group .
OMP stained positive cells in the olfactory epithelium of allergic rhinitis with olfactory disorder were significantly lower than those in the control group ( P0.05 ) .

3 . On the 7th day after drug intervention , the expression of OMP positive cells increased and the number of OMP positive cells increased and the number of OMP positive cells increased significantly ( P0.05 ) .

4 . On the 14th day after drug intervention , the expression of OMP was similar to that of Buchenne in Group 2 after drug intervention , and the expression of OMP was similar to that of compound betaxella in group 2 . There was no significant difference in the number of OMP positive cells ( P0.05 ) .

Conclusion

1 . In the model of allergic rhinitis , 75.3 % of the mice were accompanied by olfactory dysfunction . The olfactory dysfunction was a common symptom of AR .

2 . Allergic rhinitis caused morphological changes in the olfactory mucosa of mice , olfactory cortex became thinner , and the number of olfactory sensory neurons ( ORNs ) was reduced . Allergic rhinitis could reduce the expression of OMP in the olfactory mucosa of mice and reduce the number of ORNs .

3 . Both administration routes can increase the expression of OMP in the olfactory mucosa of allergic rhinitis mice , increase the number of ORNs , and the therapeutic effect can be maintained for some time after drug withdrawal .

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The effects of glucocorticoid on the expression of OMP in olfactory mucosa of allergic rhinitis mice were investigated by systemic and local administration routes .

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R765.21

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