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槲皮素通过TLR4/IRAK4/NF-κB信号通路对过敏性鼻炎大鼠炎症反应的影响
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| 篇名： | 槲皮素通过TLR4/IRAK4/NF-κB信号通路对过敏性鼻炎大鼠炎症反应的影响 |
| TITLE： | Effects of quercetin on inflammatory response in allergic rhinitis rats through TLR4/IRAK4/NF-κB signaling pathway |
| 摘要： | 目的 基于Toll样受体4/白细胞介素1（IL-1）受体相关激酶/核因子κB（TLR4/IRAK4/NF-κB）信号通路，探讨槲皮素对过敏性鼻炎（AR）大鼠炎症反应的影响及机制。方法采用卵白蛋白致敏法构建AR大鼠模型。将48只造模成功的大鼠随机分为AR组，槲皮素低、高剂量组（灌胃17.5、35mg/kg），槲皮素高剂量+TLR4激活剂（脂多糖）组（灌胃35mg/kg槲皮素+尾静脉注射0.4mg/kg脂多糖），每组12只；另取12只正常健康大鼠作为对照组，每天给药1次，连续21d。末次给药后，对各组大鼠鼻炎症状进行评分，检测血清中免疫球蛋白E（IgE）、组胺（HIS）及炎症因子水平，检测全血中调节性T细胞（Treg）、辅助性T细胞17（Th17）比例并计算Th17/Treg比值，观察大鼠鼻黏膜组织病理情况，并检测大鼠鼻黏膜组织中TLR4/IRAK4/NF-κB信号通路相关蛋白表达。结果与Control组比较，AR组大鼠鼻黏膜组织损伤严重，上皮细胞出现部分脱落、杯状细胞增生及炎症细胞浸润等情况；鼻炎症状评分，IgE、HIS、IL-17水平，Th17比例，Th17/Treg比值、p-IRAK4/IRAK4、p-NF-κBp65/NF-κBp65比值，TLR4蛋白相对表达量均显著升高（P＜0.05）；IL-10水平及Treg比例均显著降低（P＜0.05）。与AR组比较，槲皮素低、高剂量组大鼠鼻黏膜组织病理情况以及上述指标均明显改善（P＜0.05）；而加入脂多糖后，可逆转高剂量槲皮素对鼻黏膜组织病理损伤及上述指标的改善作用（P＜0.05）。结论槲皮素可通过抑制TLR4/IRAK4/NF-κB信号通路活性来抑制AR大鼠炎症反应。 |
| ABSTRACT： | OBJECTIVE To investigate the effects and mechanism of quercetin （QUE） on inflammatory response in allergic rhinitis （AR） model rats based on Toll-like receptor 4/interleukin 1 （IL-1） receptor-associated kinase/nuclear factor κB （TLR4/ IRAK4/NF-κB） signaling pathway. METHODS AR model rats were constructed by ovalbumin sensitization method. A total of 48 successfully constructed rats were randomly divided into AR group， QUE-L and QUE-H groups （i.g administration， 17.5， 35 mg/kg） and QUE-H+TLR4 activator lipopolysaccharide （LPS） group （i.g administration of 35 mg/kg QUE+intravenous administration of 0.4 mg/kg LPS via tail vein）， with 12 rats in each group. Another 12 normal healthy rats were selected as control group， once a day， for 21 consecutive days. After the last medication， rhinitis symptoms of rats in each group were scored. The serum levels of immunoglobulin E （IgE）， histamine （HIS）， and inflammatory factors were all detected. The proportions of regulatory T cells （Treg） and helper T cells 17 （Th17） cells in blood were detected， the Th17/Treg ratio was calculated， and the pathological condition of nasal mucosal tissue was observed. The expressions of TLR4/IRAK4/NF-κB pathway related protein in nasal mucosal tissue were determined. RESULTS Compared with control group， nasal mucosal tissue damage in the AR group was more severe， with partial shedding of epithelial cells， the proliferation of goblet cells， and obvious inflammatory cell infiltration. The rhinitis symptom score， the levels of IgE， HIS and IL-17， Th17 proportion， Th17/Treg ratio，p-IRAK4/IRAK4 and p-NF-κB p65/NF-κB p65 ratios as well as relative expression of TLR4 protein were increased significantly （P＜0.05）， while IL-10 level and Treg proportion were decreased significantly （P＜0.05）. Compared with AR group， the pathological injuries of nasal mucosa and the above indexes in QUE-L and QUE-H groups were all improved significantly （P＜0.05）. LPS treatment could reverse the improvement effects of high-dose QUE on histopathological damage to nasal mucosa tissue and the aforementioned indicators （P＜ 0.05）. CONCLUSIONS QUE can inhibit the inflammatory response in AR rats by inhibiting TLR4/IRAK4/NF- κB signaling pathway. |
| 期刊： | 2025年第36卷第07期 |
| 作者： | 雷西熙；邓可斌；姜锐 |
| AUTHORS： | LEI Xixi，DENG Kebin，JIANG Rui |
| 关键字： | 槲皮素；TLR4/IRAK4/NF-κB信号通路；过敏性鼻炎；炎症反应；作用机制 |
| KEYWORDS： | quercetin； TLR4/IRAK4/NF-κB signaling pa- |
| 阅读数： | 3 次 |
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