橙皮苷通过抑制NF-κB激活并恢复鼻上皮屏障功能减轻过敏性鼻炎

文献信息

中文摘要

本研究在卵清蛋白（OVA）诱导的小鼠模型中评价橙皮苷（HES）对过敏性鼻炎（AR）的治疗作用。通过OVA诱导BALB/c小鼠AR后，通过行为学评分评估过敏反应的严重程度。采用ELISA测定OVA特异性IgE、组胺和IL-6水平。采用ELISA、组织病理学染色、免疫组织化学（IHC）和Western blot检测病理变化、肥大细胞浸润和蛋白表达。使用人鼻上皮细胞（RPMI-2650），通过跨上皮电阻（TEER）和FITC-葡聚糖通透性实验评估上皮屏障功能。结果表明，HES干预后，小鼠擦鼻和打喷嚏频率显著降低，血清OVA特异性IgE、组胺和IL-6水平也显著降低。此外，HES可减轻鼻黏膜上皮损伤和炎症细胞浸润，同时减少肥大细胞聚集。HES还抑制p-p65和p-IκBα的表达，同时增强ZO-1和Occludin的蛋白表达。体外实验表明，HES可逆转OVA在HNEpC细胞中诱导的TEER降低、FITC-葡聚糖通透性增加以及ZO-1和Occludin表达降低。然而，当TNF-α激活NF-κB通路时，HES的保护作用显著减弱。总之，HES可通过抑制NF-κB信号通路的激活、减轻炎症反应并恢复鼻上皮紧密连接蛋白的表达，减轻小鼠OVA诱导的AR症状。

英文摘要

This study evaluated the therapeutic effect of hesperidin (HES) on allergic rhinitis (AR) in a mouse model induced by ovalbumin (OVA). After inducing AR in BALB/c mice through OVA, the severity of allergic reactions was assessed through behavioral scoring. The levels of OVA-specific IgE, histamine, and IL-6 were measured by ELISA. Pathological changes, mast cell infiltration, and protein expression, were detected using ELISA, histopathological staining, immunohistochemistry (IHC), and Western blot. The human nasal epithelial cells (RPMI-2650) were used and the epithelial barrier function was evaluated through transepithelial resistance (TEER) and FITC-dextran permeability assays. The results indicated that after HES intervention, the frequency of nasal rubbing and sneezing in mice significantly decreased, and the levels of serum OVA-specific IgE, histamine, and IL-6 also significantly reduced. Additionally, HES could alleviate nasal mucosal epithelial damage and inflammatory cell infiltration, while reducing mast cell aggregation. HES also inhibited the expression of p-p65 and p-IκBα, while enhancing the protein expression of ZO-1 and Occludin. In vitro experiments showed that HES could reverse the decrease in TEER, increase in FITC-dextran permeability, and decrease in ZO-1 and Occludin expression induced by OVA in HNEpC cells. However, when the NF-κB pathway was activated by TNF-α, the protective effect of HES was significantly diminished. In conclusion, HES could alleviate OVA-induced AR symptoms in mice by inhibiting the activation of the NF-κB signaling pathway, reducing inflammatory responses, and restoring the expression of tight junction proteins in the nasal epithelium.