Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Int Immunopharmacol. 2021 Mar;92:107368. doi: 10.1016/j.intimp.2021.107368. Epub 2021 Jan 14.
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.
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.
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.
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.
嗅觉功能障碍（OD）是变应性鼻炎（AR）的常见症状，可严重影响患者的生活质量；然而，其相关发病机制尚不清楚。本研究旨在探讨 OD 与 AR 中嗅球（OB）损伤的关系。评估了选择性 TLR4 抑制剂 TAK-242 治疗 OD 的潜力。
用卵清蛋白（OVA）建立 AR 小鼠模型，用埋藏食物颗粒试验（BFPT）测试 AR 小鼠的嗅觉功能。用 TAK-242 或 1% DMSO（载体）对 OD 小鼠进行腹腔注射。用免疫组织化学检测 OB 中小胶质细胞和星形胶质细胞的激活。用 TUNNEL 染色检测 OB 中的细胞凋亡。用 Western blot 检测 TLR4 信号通路中的蛋白。用 RT-PCR 检测 OB 中促炎因子 mRNA 的水平。
OD 组 OB 中观察到神经炎症，表现为胶质细胞激活和促炎因子表达增加。OD 组 OB 中细胞凋亡数量明显增加。OD 组 OB 中 TLR4、MyD88 和 p-NF-κBp65 的表达明显上调。TAK-242 治疗可显著降低 OB 中 IL-1β、IL-6 和 TNF-α mRNA 表达水平，以及 OB 组织中小胶质细胞和星形胶质细胞的激活。
TAK-242 主要通过减少 OB 中的神经炎症和细胞凋亡来改善 AR 小鼠的嗅觉功能，这可能与阻断 TLR4/MyD88/NF-κB 信号通路有关。
