黄芪多糖通过TLR4/MyD88信号通路调节Th1/Th2失衡改善大鼠过敏性鼻炎OA
Astragalus Polysaccharides Ameliorate Allergic Rhinitis in Rats by Modulating Th1/Th2 Imbalance via the TLR4/MyD88 Signaling Pathway
[目的]探讨黄芪多糖对过敏性鼻炎(AR)大鼠的治疗作用及机制.[方法]采用卵清蛋白(OVA)和氢氧化铝腹腔注射联合卵清蛋白局部鼻部刺激法建立过敏性鼻炎大鼠模型.将建模成功的大鼠随机分为模型组,地塞米松组,黄芪多糖低、高剂量组,每组10只.另选10只健康大鼠作为正常组.分别在治疗前和治疗结束后评估各组大鼠鼻部过敏症状总积分.治疗结束后,采用苏木精-伊红(HE)染色法观察鼻黏膜病理组织形态,酶联免疫吸附分析(ELISA)法检测血清γ干扰素(IFN-γ)、白细胞介素4(IL-4)、IFN-γ/IL-4、免疫球蛋白E(IgE)水平,蛋白免疫印迹(Western Blot)法检测鼻黏膜组织中T细胞表达的T-box蛋白(T-bet)、GATA结合蛋白3(GATA-3)和Toll样受体4(TLR4)/髓样分化因子88(MyD88)信号通路相关蛋白表达水平.[结果]与正常组比较,模型组大鼠鼻黏膜细胞大量脱落,黏膜下层周围腺体增生,水肿和嗜酸性粒细胞浸润,症状总积分及IL-4、IgE、GATA-3、TLR4、MyD88、磷酸化的核因子κB(p-NF-κB)水平显著升高(P＜0.05),IFN-γ、IFN-γ/IL-4、T-bet水平显著降低(P＜0.05);与模型组比较,地塞米松组及黄芪多糖低、高剂量组鼻黏膜组织水肿和炎性细胞浸润程度减轻,上皮细胞脱落较少,鼻黏膜组织结构较为完整,症状总积分及IL-4、IgE、GATA-3、TLR4、MyD88、p-NF-κB水平显著降低(P＜0.05),IFN-γ、IFN-γ/IL-4、T-bet水平显著升高(P＜0.05);与地塞米松组比较,黄芪多糖低、高剂量组症状总积分及IL-4、IgE、GATA-3、TLR4、MyD88、p-NF-κB水平显著降低(P＜0.05),IFN-γ、IFN-γ/IL-4、T-bet水平显著升高(P＜0.05).[结论]黄芪多糖能够有效改善过敏性鼻炎大鼠鼻部过敏症状,抑制炎症反应,调节免疫功能,其作用机制与TLR4/MyD88信号通路介导的Th1/Th2失衡有关.
Objective To investigate the therapeutic effect and mechanism of Astragalus polysaccharides(APS)on allergic rhinitis(AR)in rats.Methods An AR model was established by intraperitoneal injection of ovalbumin(OVA)and aluminum hydroxide combined with local nasal stimulation with OVA.Successfully modeled rats were randomly divided into a model group,a dexamethasone group,low-dose APS group and high-dose APS group,with 10 rats per group.An additional 10 healthy rats were selected as the normal group.The total score of nasal allergic symptom was assessed before and after treatment.After treatment,histopathological feature in the nasal mucosa were observed by hematoxylin-eosin(HE)staining;serum levels of interferon-gamma(IFN-γ),interleukin-4(IL-4),IFN-γ/IL-4 ratio,and immunoglobulin E(IgE)were detected by enzyme-linked immunosorbent assay(ELISA);and protein expression levels of T-bet,GATA-binding protein 3(GATA-3),and proteins related to the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway in nasal mucosal tissue were measured by Western Blot.Results Compared with the normal group,the model group exhibited massive exfoliation of nasal mucosal cells,hyperplasia of periglandular tissue in the submucosa,edema,eosinophil infiltration,significantly increased total symptom scores and levels of IL-4,IgE,GATA-3,TLR4,MyD88,and phosphorylated nuclear factor-kappa B(p-NF-κB)(P＜0.05),and significantly decreased levels of IFN-γ,IFN-γ/IL-4 ratio,and T-bet(P＜0.05).Compared with the model group,the dexamethasone group and the low-and high-dose APS groups showed reduced nasal mucosal edema and inflammatory cell infiltration,less epithelial exfoliation,and a more intact nasal mucosal structure,along with significantly decreased total symptom scores and levels of IL-4,IgE,GATA-3,TLR4,MyD88,and p-NF-κB(P＜0.05),and significantly increased levels of IFN-γ,IFN-γ/IL-4 ratio,and T-bet(P＜0.05).Compared with the dexamethasone group,the low-dose and high-dose APS groups showed significantly lower total symptom scores and levels of IL-4,IgE,GATA-3,TLR4,MyD88,and p-NF-κB(P＜0.05),and significantly higher levels of IFN-γ,IFN-γ/IL-4 ratio,and T-bet(P＜0.05).Conclusion Astragalus polysaccharides can effectively alleviate nasal allergic symptoms,inhibit inflammatory responses,and regulate immune function in AR rats.The mechanism is associated with the modulation of TLR4/MyD88 signaling pathway-mediated Th1/Th2 imbalance
陈进伟;孙继周;蒋源;张仕林
西电集团医院耳鼻咽喉科,陕西 西安 710077西电集团医院耳鼻咽喉科,陕西 西安 710077西电集团医院耳鼻咽喉科,陕西 西安 710077西电集团医院耳鼻咽喉科,陕西 西安 710077
医药卫生
黄芪多糖过敏性鼻炎TLR4/MyD88信号通路Th1/Th2失衡大鼠
Astragalus polysaccharidesallergic rhinitis(AR)TLR4/MyD88 signaling pathwayTh1/Th2 in balancerats
《广州中医药大学学报》 2026 (2)
456-462,7
陕西省重点研发计划项目(编号:2021SF-379)
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