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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
                                Δ


          雷西熙 ,邓可斌,姜 锐(湖北省中医院耳鼻喉科,武汉 430006)
                *
                                 #
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)07-0832-05
          DOI  10.6039/j.issn.1001-0408.2025.07.11

          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、35 mg/kg),槲皮素高剂量+TLR4 激活剂(脂多糖)组(灌胃 35 mg/kg 槲皮素+尾静脉注射
          0.4 mg/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21 d。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-κB p65/NF-κB p65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。
          关键词  槲皮素;TLR4/IRAK4/NF-κB信号通路;过敏性鼻炎;炎症反应;作用机制

          Effects of quercetin on inflammatory response in allergic rhinitis rats through TLR4/IRAK4/NF-κB signaling
          pathway
          LEI Xixi,DENG Kebin,JIANG Rui(Dept.  of  Otolaryngology,  Hubei  Provincial  Hospital  of Traditional Chinese
          Medicine, Wuhan 430006, China)

          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
              Δ 基金项目 湖 北 省 卫 生 健 康 委 员 会 中 医 药 科 研 项 目(No.
                                                              response  in  AR  rats  by  inhibiting  TLR4/IRAK4/NF- κB
          ZY2021Z001)                                         signaling pathway.
             *第一作者 主治医师,硕士。研究方向:中西医结合治疗耳鼻喉
          疾病。E-mail:kvbs2f@163.com                            KEYWORDS    quercetin;  TLR4/IRAK4/NF- κB  signaling  pa-
              # 通信作者 副主任医师。研究方向:耳鼻咽喉疾病。E-mail:                thway;  allergic  rhinitis;  inflammatory  response;  action  of
          y60iov3@163.com                                     mechanism


          · 832 ·    China Pharmacy  2025 Vol. 36  No. 7                               中国药房  2025年第36卷第7期
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