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胃泌素释放肽参与小鼠变应性鼻炎的形成。

Gastrin-Releasing Peptide Is Involved in the Establishment of Allergic Rhinitis in Mice.

作者信息

Matsumoto Yuma, Yokoi Hidenori, Kimura Toru, Matsumoto Yoshifumi, Kawada Michitsugu, Arae Ken, Nakae Susumu, Ikeda Tetsuya, Matsumoto Kenji, Sakurai Hiroyuki, Saito Koichiro

机构信息

Department of Otorhinolaryngology, Kyorin University School of Medicine, Tokyo, Japan.

Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.

出版信息

Laryngoscope. 2018 Nov;128(11):E377-E384. doi: 10.1002/lary.27394. Epub 2018 Aug 27.

Abstract

OBJECTIVE

Gastrin-releasing peptide (GRP) is a neuropeptide that targets transmembrane-type receptors. Its role in allergic rhinitis (AR) has yet to be investigated. The present study utilized the nasal mucosa of AR model mice to examine GRP and GRP receptor (GRPR) expression levels, localization, and other factors to evaluate their role in AR pathology.

STUDY DESIGN

In vivo study in an animal model.

METHODS

GRP and GRPR expression levels were examined in three different AR models established in BALB/c mice. In addition, a GRPR antagonist (RC-3095) was administered to AR mice to investigate its effect. The distribution of GRPR expression on mast cells in the nasal mucosa with AR was examined. Finally, we investigated the inhibitory effect of RC-3095 on allergy symptoms induced by histamine.

RESULTS

GRP and GRPR were highly expressed in the nasal mucosal epithelium and interstitial tissues surrounding the nasal glands in AR groups according to immunostaining. GRP and GRPR expression as determined by western blotting increased in the nasal mucosa as the degree of nasal sensitization increased. In addition, the average counts of sneezing and nasal rubbing after treatment in the AR + RC-3095 group were significantly lower than those in the AR + nasal saline group. Mast cells often colocalized with GRPR around nasal glands. Moreover, RC-3095 was effective in reducing sneezing induced by histamine.

CONCLUSION

The GRP-GRPR system is likely to be involved in allergic inflammation. This system may represent a novel therapeutic target for refractory AR.

LEVEL OF EVIDENCE

NA. Laryngoscope, E377-E384, 2018.

摘要

目的

胃泌素释放肽(GRP)是一种作用于跨膜型受体的神经肽。其在变应性鼻炎(AR)中的作用尚未得到研究。本研究利用AR模型小鼠的鼻黏膜来检测GRP和GRP受体(GRPR)的表达水平、定位及其他因素,以评估它们在AR病理过程中的作用。

研究设计

在动物模型中进行的体内研究。

方法

检测在BALB/c小鼠中建立的三种不同AR模型中GRP和GRPR的表达水平。此外,给AR小鼠施用GRPR拮抗剂(RC-3095)以研究其作用。检测AR鼻黏膜中肥大细胞上GRPR表达的分布。最后,我们研究了RC-3095对组胺诱导的过敏症状的抑制作用。

结果

免疫染色显示,AR组鼻黏膜上皮及鼻腺周围的间质组织中GRP和GRPR高表达。蛋白质印迹法测定显示,随着鼻敏化程度增加,鼻黏膜中GRP和GRPR表达增加。此外,AR+RC-3095组治疗后打喷嚏和擦鼻的平均次数显著低于AR+生理盐水组。肥大细胞常与鼻腺周围的GRPR共定位。此外,RC-3095能有效减少组胺诱导的打喷嚏。

结论

GRP-GRPR系统可能参与变应性炎症。该系统可能是难治性AR的一个新的治疗靶点。

证据水平

无。《喉镜》,E377-E384,2018年。

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