Objective

Olfactory dysfunction (OD) is a common symptom of allergic rhinitis (AR) that can seriously affect patient quality of life; however, the associated pathogenesis remains unclear. This study aimed to explore the relationship between OD and damage of the olfactory bulb (OB) in allergic rhinitis (AR). The therapeutic potential of TAK-242, a selective TLR4 inhibitor, was evaluated for OD.

Method

An AR mouse model was established with ovalbumin (OVA) to test the olfactory function of AR mice using the buried food pellet test (BFPT). Mice with OD were intraperitoneally injected with TAK-242 or 1% DMSO (vehicle). Immunohistochemistry was used to detect microglia and astrocyte activation in the OB. TUNNEL staining was performed to detect apoptosis in the OB. Proteins in the TLR4 signaling pathway were detected by Western blot. The level of proinflammatory factor mRNA in the OB was determined by RT-PCR.

Result

Neuroinflammation was observed in the OB of the OD group, as evidenced by glial cell activation and increased proinflammatory factor expression. The number of apoptotic cells was significantly increased in the OB of the OD group. The expression of TLR4, MyD88, and p-NF-κBp65 was significantly up-regulated in the OB of the OD group. TAK-242 treatment significantly reduced the level of IL-1β, IL-6, and TNF-α mRNA expression, as well as activation of microglia and astrocytes in the OB tissues.

Conclusion

TAK-242 improve olfactory function in AR mice mainly by reducing neuroinflammation and apoptosis in the OB, which may be related to blocking the TLR4/MyD88/NF-κB signaling pathway.

中文翻译：

---

TAK-242通过抑制嗅球中的神经炎症来改善变应性鼻炎小鼠模型中的嗅觉功能障碍

目的

嗅觉障碍（OD）是变应性鼻炎（AR）的常见症状，会严重影响患者的生活质量。然而，相关的发病机制仍不清楚。本研究旨在探讨变应性鼻炎（AR）中OD与嗅球（OB）损伤之间的关系。评估了选择性TLR4抑制剂TAK-242的治疗潜力。

方法

建立了带有卵白蛋白（OVA）的AR小鼠模型，以使用掩埋食物颗粒试验（BFPT）测试AR小鼠的嗅觉功能。OD小鼠腹膜内注射TAK-242或1％DMSO（载体）。免疫组织化学用于检测OB中的小胶质细胞和星形胶质细胞活化。进行TUNNEL染色以检测OB中的细胞凋亡。通过Western印迹检测TLR4信号传导途径中的蛋白质。通过RT-PCR确定OB中促炎因子mRNA的水平。

结果

在OD组的OB中观察到神经炎症，这由神经胶质细胞激活和促炎因子表达增加所证明。在OD组的OB中，凋亡细胞的数量显着增加。OD组的OB中TLR4，MyD88和p-NF-κBp65的表达显着上调。TAK-242治疗可显着降低OB组织中IL-1β，IL-6和TNF-αmRNA的表达水平以及小胶质细胞和星形胶质细胞的活化。

结论

TAK-242主要通过减少OB中的神经炎症和凋亡来改善AR小鼠的嗅觉功能，这可能与阻断TLR4 / MyD88 /NF-κB信号通路有关。