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信号素 3A 的经鼻给药可缓解变应性鼻炎小鼠模型的打喷嚏和鼻蹭。

Intranasal administration of semaphorin-3A alleviates sneezing and nasal rubbing in a murine model of allergic rhinitis.

机构信息

Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University, Japan.

出版信息

J Pharmacol Sci. 2011;117(1):34-44. doi: 10.1254/jphs.11005fp. Epub 2011 Aug 18.

Abstract

Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis (AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A (Sema3A) has been previously shown to restrict innervation of sensory neurons, it is presumed that reduced Sema3A expression in the nasal mucosa might contribute to the hypersensitivity. Analysis of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression of Sema3A in the nasal epithelium, which was accompanied by an increased nerve fiber density in the lamina propria of the turbinate. In rescue experiments, intranasal administration of recombinant Sema3A in the AR model mice alleviated sneezing and nasal rubbing symptoms. In addition, histological examinations also revealed that nerve fiber density was decreased in the lamina propria of the Sema3A-treated nasal turbinate. These results suggest that the nasal hypersensitivity of AR may be attributed to reduction of Sema3A expression and intranasal administration of Sema3A may provide a novel approach to alleviate the allergic symptoms for AR treatment.

摘要

打喷嚏和持续的鼻腔瘙痒是过敏性鼻炎(AR)的令人痛苦的症状。最近的研究表明,鼻甲骨感觉神经元的过度神经支配是打喷嚏和瘙痒的根本原因之一。由于 Semaphorin-3A(Sema3A)先前已被证明可以限制感觉神经元的支配,因此可以假设鼻黏膜中 Sema3A 表达的减少可能导致过敏反应过度。对卵清蛋白致敏的 AR 小鼠模型的分析表明,鼻上皮中的 Sema3A 表达减少,同时鼻甲骨固有层中的神经纤维密度增加。在挽救实验中,在 AR 模型小鼠中鼻内给予重组 Sema3A 可缓解打喷嚏和鼻擦症状。此外,组织学检查还表明,Sema3A 处理的鼻甲骨固有层中的神经纤维密度降低。这些结果表明,AR 的鼻过敏可能归因于 Sema3A 表达的减少,鼻内给予 Sema3A 可能为缓解 AR 的过敏症状提供一种新方法。

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