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Effectiveness of Betamethasone in Treating Mice with Olfactory Dysfunction from Allergic Rhinitis
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摘要:
目的 观察变应性鼻炎(allergic rhinitis, AR)对嗅觉功能的影响及倍他米松对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(buried food test, BFT)评估AR小鼠嗅觉功能, HE染色及免疫组化方法观察AR小鼠嗅黏膜组织形态学变化及嗅觉标记蛋白(olfactory marker protein, OMP)表达的变化。腹腔内注射复方倍他米松, 分别在干预后第7及14天应用免疫组化方法检测AR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, 74.55%的AR小鼠伴有嗅觉障碍。AR小鼠嗅黏膜上皮层较对照组明显变薄, 嗅感受神经元(olfactory receptor neurons, ORNs)层数减少、排列紊乱。AR小鼠嗅黏膜OMP表达亦较对照组减少, 其中AR伴嗅觉障碍组嗅上皮OMP染色阳性细胞数为39.77±2.012, 与对照组66.38±1.517比较, 差异有统计学意义(P < 0.05);但AR不伴嗅觉障碍组嗅上皮OMP染色阳性细胞数为59.50±0.558, 与对照组比较差异无统计学意义(P > 0.05)。复方倍他米松干预1组小鼠嗅黏膜OMP表达增加, 已接近对照组水平, 为62.04±1.227, 与不用药组47.34±1.809比较差异有统计学意义(P < 0.05)。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, 两组OMP染色阳性细胞数比较差异无统计学意义(P > 0.05)。 结论 AR引起嗅觉障碍的作用机制除鼻腔气道阻塞原因外, 嗅黏膜本身因炎症发生变化也是重要原因。全身应用糖皮质激素可对嗅黏膜产生影响, 是治疗AR引发嗅觉障碍的有效方法。 Abstract:Objective To explore the impact of allergic rhinitis (AR) on olfactory function and observe the effectiveness of betamethasone in treating mice with olfactory dysfunction. Methods Mouse AR models were established by intraperitoneal injection and intranasal application of ovalubumin. The olfactory function of the mice was evaluated by buried food test (BFT). The expression of olfactory marker protein (OMP) in the olfactory mucosa was tested by immunohistochamistry. The expression of OMP in the olfactory mucosa was observed 7 and 14 days after intraperitoneal application of betamethasone. Results The incidence of olfactory dysfunction in AR mice was 74.55%. The olfactory epithelium became thinner in AR mice than in control group. The down-regulation of OMP in olfactory epithelium was observed in AR mice compared with control group. The number of OMP-positive cells was 66.38±1.517 in control group and 59.50±0.558 in group without olfactory dysfunction (P > 0.05). The number of OMP-positive cells was 39.77±2.012 in group with olfactory dysfunction, which was significantly different compared with control group and the group with olfactory dysfunction (P < 0.05). The number of OMP-positive cells was 62.04±1.227 in betamethasone group 1, which was significantly higher than that in the non-medication group (47.34±1.809) (P < 0.05); meanwhile, it showed no significant difference between betamethasone group 1 and the control group (P > 0.05). The number of OMP-positive cells was 63.82±1.254 in betamethasone group 2, and the expression of OMP in betamethasone group 2 was similar to that in betamethasone group 1. Conclusions AR-associated olfactory dysfunction is not only due to the blockage of nasal cavity but also the change in mucosa by inflammation. Systemic application of betamethasone is an effective method in treating AR-associated olfactory dysfunction. -
Key words:
- allergic rhinitis /
- olfactory /
- glucocorticoid /
- olfactory marker protein /
- animal model
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图 5 免疫组化示各组小鼠嗅黏膜嗅觉标记蛋白表达(× 400)
A.对照组; B.变应性鼻炎不伴嗅觉障碍组; C.变应性鼻炎伴嗅觉障碍组; D.不用药组; E.复方倍他米松干预1组; F.复方倍他米松干预2组
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[1] 倪道凤.嗅觉障碍和嗅觉功能检查[J].临床耳鼻咽喉科杂志, 2003, 17:571-575. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=lcebyhkzz200309044 [2] Stenner M, Vent J, Huttenbrink KB, et al. Topical therapy in anosmia:relevance of steroid-responsiveness[J]. Laryngoscope, 2008, 118:1681-1686. doi: 10.1097/MLG.0b013e31817c1368 [3] Kirtsrccsakul V, Naclcrio RM. Role of allergy in rhinosinusitis[J]. Curr Opin Allery Clin Immunol, 2004, 4:17-23. doi: 10.1097/00130832-200402000-00005 [4] Moll B, Klimek L, Eggers G. Comparison of olfactory function in patients with seasonal and perennial allergic rhinitis[J]. Allergy, 1998, 53:297-301. doi: 10.1111/j.1398-9995.1998.tb03890.x [5] Cowart BJ, Flynn-Rodden K, McGeady SJ. Hyposmia in allergic rhinitis[J]. J Allergy Clin Immunol, 1993, 91:747-751. doi: 10.1016/0091-6749(93)90194-K [6] Rombaux P, Collet S, Eloy P. Smell disorders in ENT clinic[J]. BENT, 2005, 1(Supl 1):97-107. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=https://www.jstage.jst.go.jp/article/jjrhi/59/1/59_1/_article/-char/en [7] Doty RL, Mishra A. Olfactory and its alteration by nasal obstruction rhinitis and rhinosinusitis[J]. Laryngoscope, 2001, 111:409-423. doi: 10.1097/00005537-200103000-00008 [8] Faulcon P, Biacabe B, Bonfils P. Contribution of corticosteroid treatment in neurosensorial anosomia:a series of 62 patients[J]. Ann Otolaryngol Chir Cervicofac, 2000, 117:374-377. http://www.ncbi.nlm.nih.gov/pubmed/11148341 [9] Heilmann S, Huettenbrink KB, Hummel T. Local and systemic administration of corticosteroid in the treatment of olfactory loss[J]. Am J Rhinol, 2004, 18:29-33. doi: 10.1177/194589240401800107 [10] Stevens MH. Steroid-dependent anosmia[J]. Laryngoscope, 2001, 111:200-203. doi: 10.1097/00005537-200102000-00002 [11] 倪道凤.嗅觉基础与临床[M].北京:人民卫生出版社, 2010:186, 204. [12] 关静, 倪道凤, 王剑, 等.上呼吸道感染和鼻部炎症性疾病嗅觉障碍的治疗[J].临床耳鼻咽喉头颈外科杂志, 2010, 24:485-488. http://doi.med.wanfangdata.com.cn/qk/lcebyhkzz201011002 [13] Miescher SM, Vogel M. Molecular aspects of allergy[J]. Mol Aspects Med, 2003, 23:413-462. [14] 顾之燕.呼吸道炎症反应[J].中华耳鼻咽喉科杂志, 2001, 36:397-399. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhebyhk200105036 [15] Amit A, Saxena VS, Pratibha N, et al. Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition, antihistaminic and antispasmodic activities of Aller-7, a novel botanical formulation for allergic rhinitis[J]. Drugs Exp Clin Res, 2003, 29:107-115. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=0a0d672a26b9ad7360d47268f9a5c962 [16] Mott AE, Cain WS, Lafreniere D. Topical corticosteroid treatment of anosmia associated with nasal and sinus disease[J]. Arch Otolaryngol Head Neck Surg, 1997, 123:367-372. doi: 10.1001/archotol.1997.01900040009001 [17] Simola M, Malmberg H. Sense of smell in allergic and nonallergic rhinitis[J]. Allergy, 1998, 53:190-194. doi: 10.1111/j.1398-9995.1998.tb03869.x [18] Takahashi N, Aramaki Y, Tsuchiy S. Allergic rhinitis model with Brown Norway rat and evaluation of antiallergic drugs[J]. J Pharmacobiodyn, 1990, 13:414-420. doi: 10.1248/bpb1978.13.414 [19] Nakaya M, Dohi M, Okunishi K, et al. Noninvasive system for evaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis[J]. Lab Invest, 2006, 86:917-926. doi: 10.1038/labinvest.3700452 [20] Tanaka K, Okamoto Y. A nasal allergy model developed in the guinea pig by application of 2, 4-toluene diisocyanate[J]. Int Allergy Appl Immunol, 1998, 85:392-397. http://onlinelibrary.wiley.com/resolve/reference/XREF?id=10.1159/000234540 [21] Sehmi R, Wood LJ, Watson R, et al. Allergen-induced increases in IL-5 receptor alpha-subunit expression om bone marrow-derived CD34+ cell from asthmatic subjects. A novel marker of progenitor cell commitment towards eosinophilic differentiation[J]. J Clin Invest, 1997, 100:2466-2475. doi: 10.1172/JCI119789 [22] 林静, 魏永祥, 王向东, 等.变应性鼻炎伴嗅觉障碍小鼠嗅黏膜的观察[J].中国耳鼻咽喉头颈外科, 2008, 15:465-468. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=ebyhtjwk200808009 [23] Nathan BP, Yost J, Litherland MT, et al. Olfactory function in spoE knockout mice[J]. Behav Brain Res, 2004, 150:1-7. doi: 10.1016/S0166-4328(03)00219-5 [24] Liebenauer LL, Slotnick BM. Social organization and ag-gression in a group of olfactory bulbectomized male mice[J]. Physiol Behav, 1996, 60:403-409. http://www.sciencedirect.com/science/article/pii/S0031938496800114 [25] Allen M, Seiden HJ. The diagnosis of a conductive olfactory loss[J]. Laryngoscope, 2001, 111:9-14. doi: 10.1097/00005537-200101000-00002 [26] Berghard A, Buck LB, Liman ER. Evidence for distinct signaling mechanisms in two mammalian olfactory sense organ[J]. Proc Natl Acad Sci USA, 1996, 93:2365-2369. doi: 10.1073/pnas.93.6.2365 [27] Buck LB. The molecular architecture of odor and pheromone sensing in mammals[J]. Cell, 2000, 100:611-618. doi: 10.1016/S0092-8674(00)80698-4 [28] 陈志宏, 倪道凤.气味受体研究进展[J].国外医学耳鼻咽喉科学分册, 2003, 27:92-95. [29] Hummel T, Rissom K, Reden J, et al. Effects of olfactory training in patients with olfactory loss[J]. Laryngoscope, 2009, 119:496-499. http://europepmc.org/abstract/med/19235739 [30] Henkin RI, Potolicchio SJ Jr, Levy LM. Improvement in smell and taste dysfunction after repetitive transcranial magnetic stimulation[J]. Am J Otolarnygol, 2011, 32:38-46. doi: 10.1016/j.amjoto.2009.10.001 [31] Hotchkiss WT. Influence of prednisone on nasal polyposis with anosmia:preliminary report[J]. AMA Arch Otolaryngol, 1995, 64:478-479. [32] Fukazawa K, Fujii M, Tomofuji S, et al. Local injection of dexamethasone acetate suspension into the nasal mucosa in cases of olfactory disturbance[J]. Nippon Jibinkoka Gakkai Kaiho, 1999, 102:1175-1183. doi: 10.3950/jibiinkoka.102.1175 [33] Seo BS, Lee HJ, Mo JH, et al. Treatment of postviral olfactory loss with glucocorticoids, Ginkgo biloba, and mometasone nasal spray[J]. Arch Otolaryngol Head Neck Surg, 2009, 135:1000-1004. doi: 10.1001/archoto.2009.141 [34] Lee GS, Cho JH, Park CS, et al. The effect of Ginkgo biloba on the expression of intermediate-early antigen (c-fos) in the experimentally induced anosmic mouse[J]. Auris Nasus Larynx, 2009, 36:287-291. doi: 10.1016/j.anl.2008.08.004 [35] Robinson AM, Kern RC, Foster JD. Expression of glucocorticoid receptor mRNA and protein in the olfactory mucosa:physiologic and pathophysiologic implications[J]. Laryngoscope, 1998, 108:1238-1242. doi: 10.1097/00005537-199808000-00026 [36] Takanosawa M, Nishino H, Ohta Y, et al. Glucocorticoids enhance regeneration of murine olfactory epithelium[J]. Acta Otolaryngol, 2009, 129:1002-1009. doi: 10.1080/00016480802530663 [37] Wei Y, Zhang C, Miao X, et al. Effects of glucocorticoid on cyclic nucleotide-gated channels of olfactory receptor neurons[J]. J Otolaryngol Head Neck Surg, 2009, 38:90-95. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=0da98223328307bcc5ac5de50f4aa2ce -
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