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SB203580,一种 p38MAPK 抑制剂,通过抑制 AR 小鼠中嗅感觉神经元凋亡来减轻嗅觉功能障碍(p38 丝裂原活化蛋白激酶在卵清蛋白诱导的变应性鼻炎中嗅感觉神经元凋亡中的激活和作用)。

SB203580, a p38MAPK inhibitor, attenuates olfactory dysfunction by inhibiting OSN apoptosis in AR mice (activation and involvement of the p38 mitogen-activated protein kinase in olfactory sensory neuronal apoptosis of OVA-induced allergic rhinitis).

机构信息

Department of Otolaryngology-Head and Neck Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong, China.

Department of Otolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

出版信息

Brain Behav. 2019 Jun;9(6):e01295. doi: 10.1002/brb3.1295. Epub 2019 Apr 30.

Abstract

OBJECTIVE

This study aimed to investigate the effect of the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway on olfactory mucosa function and apoptosis of olfactory sensory neurons (OSNs) in an allergic rhinitis (AR) mouse model.

METHOD

Fifty-five BALB/c mice were used to establish AR models by ovalbumin, and their olfactory function was confirmed by the buried food pellet test. Then, 28 mice with hyposmia were selected. SB203580, a p38MAPK inhibitor, and normal saline (NS) were injected into mice with olfactory defects. The olfactory function, apoptosis of OSNs in olfactory mucosa, and the expression of the olfaction marker protein (OMP), p38MAPK, and p-p38MAPK were detected after the intervention.

RESULT

SB203580 treatment significantly upregulated OMP expression and significantly improved the olfactory function of AR mice by reducing the percentage of apoptotic OSNs. In addition, SB203580 attenuated the activation of the p38MAPK signaling pathway.

CONCLUSION

SB203580 protected olfactory function in an AR mouse model. This protective effect may be associated with the antiapoptotic effects of SB203580 via the p38MAPK signaling pathway.

摘要

目的

本研究旨在探讨丝裂原活化蛋白激酶 p38(p38MAPK)信号通路对变应性鼻炎(AR)小鼠模型嗅黏膜功能和嗅感觉神经元(OSN)凋亡的影响。

方法

采用卵清蛋白建立 55 只 BALB/c 小鼠 AR 模型,通过埋藏食物颗粒试验确认嗅觉功能。然后,选择 28 只嗅觉减退的小鼠,用 p38MAPK 抑制剂 SB203580 和生理盐水(NS)对有嗅觉缺陷的小鼠进行干预,检测干预后小鼠的嗅觉功能、嗅黏膜 OSN 凋亡情况以及嗅觉标志物蛋白(OMP)、p38MAPK 和 p-p38MAPK 的表达。

结果

SB203580 治疗可显著上调 OMP 表达,通过减少凋亡 OSN 的百分比,显著改善 AR 小鼠的嗅觉功能。此外,SB203580 可抑制 p38MAPK 信号通路的激活。

结论

SB203580 可保护 AR 小鼠模型的嗅觉功能,这种保护作用可能与 SB203580 通过 p38MAPK 信号通路的抗凋亡作用有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5559/6577615/f0fb74d7c0aa/BRB3-9-e01295-g001.jpg

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