柚皮素对过敏性鼻炎模型大鼠鼻黏膜组织TLR4/NF-κB/TNF-α信号通路的影响  

Effeet of Naringenin on TLR4/NF-κB/TNF-αSignal Pathway in Nasal Mucosa of Rats with Allergic Rhinitis

作　　者：牛金明[1] 程莉雅[1] 吴美美[1] NIU Jin-ming;CHENG Li-ya;WU Mei-mei(Department of Otolaryngology,Weifang Hospital of Raditional Chinese Medicine,Weifang 261000,China)

机构地区：[1]潍坊市中医院耳鼻喉二科,山东潍坊261000

出　　处：《中国实验诊断学》2023年第4期483-488,共6页Chinese Journal of Laboratory Diagnosis

摘　　要：目的探究柚皮素对过敏性鼻炎(AR)模型大鼠鼻黏膜组织Toll样受体4(TLR4)/核因子κB(NF-κB)/肿瘤坏死因子α(TNF-α)信号通路的影响。方法建立AR大鼠模型,48只大鼠以随机数字表法平均分为4组:模型组、柚皮素低(100 mg/kg)剂量组、柚皮素高(200 mg/kg)剂量组、柚皮素高(200 mg/kg)剂量+脂多糖(LPS)(TLR4通路激活剂,0.4 mg/kg)组,另取12只SD大鼠设为对照组。以药物分组干预治疗后,观察大鼠鼻炎症状并进行评分;苏木精-伊红(HE)染色检测大鼠鼻黏膜组织病理形态改变;试剂盒测定大鼠血清IgE及炎性因子白细胞介素(IL)-17、IL-18水平;免疫组织化学染色检测大鼠鼻黏膜组织CD19、CD23表达;免疫印迹法检测大鼠鼻黏膜组织TLR4/NF-κB/TNF-α通路蛋白表达。结果与对照组相比,模型组大鼠鼻黏膜组织发生严重病理损伤,鼻炎症状评分、血清IgE、IL-17及IL-18水平、鼻黏膜组织CD19、CD23阳性细胞比例、鼻黏膜组织TLR4、核内NF-κB p65、TNF-α蛋白表达水平显著升高(P<0.05);与模型组相比,柚皮素干预组大鼠鼻黏膜组织病理损伤均减轻,鼻炎症状评分、血清IgE、IL-17及IL-18水平、鼻黏膜组织CD19、CD23阳性细胞比例、鼻黏膜组织TLR4、核内NF-κB p65、TNF-α蛋白表达水平均降低,且柚皮素高剂量组大鼠各指标改变程度更强;与柚皮素高剂量组相比,柚皮素高剂量+LPS组大鼠鼻黏膜组织病理损伤加重,鼻炎症状评分、血清IgE、IL-17及IL-18水平、鼻黏膜组织CD19、CD23阳性细胞比例、鼻黏膜组织TLR4、核内NF-κB p65、TNF-α蛋白表达水平显著升高(P<0.05)。结论柚皮素可通过抑制TLR4/NF-κB/TNF-α通路表达而减轻超敏反应及炎症,从而缓解鼻黏膜组织损伤,改善AR大鼠症状。Objective To explore the effect of naringenin on the Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-kB)/tumor necrosis factor-alpha(TNF-α)signaling pathway in the nasal mucosa tissue of allergic rhinitis(AR)model rats.Methods Forty-eight AR model rats were established and divided into four groups by random number table method:model group,naringenin low(1o0 mg/kg)dose group,naringenin high(2o0 mg/kg)dose group,and naringenin high(200 mg/kg)dose+lipopolysaccharide(LPS)(TLR4 pathway activator,0.4 mg/kg)group,another 12 SD rats were taken as the control group.After intervention treatment with drugs,the symptoms of rhinitis in rats were observed and scored;hematoxylin-eosin(HE)staining was used to detect the pathological changes of rat nasal mucosa tissue;the kit was used to measure the levels of rat serum IgE and inflammatory factors interleukin(IL)-17 and IL-18;immunohistochemical staining was used to detect the expression of CD19 and CD23 in rat nasal mucosa tissue;Western blotting was used to detect the expression of TLR4/NF-sB/TNF-αpathway protein in rat nasal mucosa tissue.Results Compared with the control group,the nasal mucosal tissue of the model group had severe pathological damage,the rhinitis symptom score,serum IgE,IL-17 and IL-18 levels,nasal mucosal tissue CD19,CD23 positive cell ratios,nasal mucosal tissue TLR4,nuclear NF-B p65,TNF-αprotein expression levels were significantly increased(P<0.05);compared with the model group,the pathological damage of the nasal mucosa of rats in naringenin intervention groups was reduced,the rhinitis symptom score,serum IgE,IL-17 and IL-18 levels,nasal mucosal tissue CD19,CD23 positive cell ratios,nasal mucosal tissue TLR4,nuclear NF-B p65,TNF-αprotein expression levels were significantly decreased,The changes of all indexes in the naringenin high-dose group were stronger;Compared with the naringenin high-dose group,the pathological damage of the nasal mucosa of rats in naringenin high dose+LPS group was aggravated,the rhinitis symptom score,serum IgE,IL-17 an

关 键 词：柚皮素 过敏性鼻炎 鼻黏膜组织 Toll样受体4/核因子κB/肿瘤坏死因子α信号通路 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]