摘要
为探讨黄芪甲苷对过敏性鼻炎(allergic rhinitis,AR)小鼠的作用及对高迁移率族蛋白B1(high mobility group box 1 protein,HMGB1)/TLR4/NF-κB信号通路的影响,采用卵清蛋白(ovalbumin,OVA)诱发C57BL/6小鼠AR,并采用低(12.5 mg/kg)、中(25.0 mg/kg)、高(50.0 mg/kg)剂量的黄芪甲苷进行治疗。研究观察小鼠的行为学变化;苏木精-伊红(hematoxylin-eosin,HE)染色观察小鼠鼻黏膜组织的病理变化;ELISA检测小鼠血清IL-4、IL-6、IL-10、IL-1β、IgE、TNF-α、细胞间黏附分子1(intercellular adhesion molecule 1,ICAM-1)和血管细胞黏附分子1(vascular cell adhesion molecule 1,VCAM-1)的浓度;Western blotting检测鼻黏膜组织HMGB1、TLR4、NF-κB及p-NF-κB蛋白表达。结果显示,AR模型小鼠出现剧烈抓鼻、打喷嚏等症状,鼻黏膜组织中炎症细胞严重浸润。黄芪甲苷治疗后,小鼠症状缓解,鼻黏膜组织中炎症细胞减少,HMGB1、TLR4和p-NF-κB蛋白表达水平及血清中IL-4、IL-6、IL-1β、IgE、TNF-α、ICAM-1和VCAM-1浓度均显著降低(P<0.05),IL-10浓度显著升高(P<0.05)。由此黄芪甲苷对AR小鼠具有较好的治疗效果,通过抑制HMGB1/TLR4/NF-κB通路减少促炎因子的产生可能是黄芪甲苷治疗AR的重要分子机制之一。
To investigate the effect of astragalosideⅣon mice with allergic rhinitis(AR)and its influence on high mobility group box 1 protein(HMGB1)/TLR4/NF-κB signaling pathway,AR was induced in C57 BL/6 mice by ovalbumin(OVA).Model mice were treated with low dose(12.5 mg/kg),medium dose(25.0 mg/kg)and high dose(50.0 mg/kg)of astragalosideⅣ.Behavior changes of mice were observed.The pathological changes of nasal mucosa were observed by hematoxylin-eosin(HE)staining.ELISA was used to detect the concentrations of IL-4,IL-6,IL-10,IL-1β,IgE,TNF-α,intercellular adhesion molecule 1(ICAM-1)and vascular cell adhesion molecule 1(VCAM-1)in serum.Western blotting was used to detect the expression levels of HMGB1,TLR4,NF-κB and p-NF-κB in nasal mucosa.The results showed that AR model mice showed severe nasal scratching and sneezing,and severe inflammatory cell infiltration in the nasal mucosa.After treatment with astragalosideⅣ,the symptoms of AR were alleviated,the infiltration of inflammatory cells in the nasal mucosa was reduced,the protein expression of HMGB1,TLR4 and p-NF-κB and levels of IL-4,IL-6,IL-1β,IgE,TNF-α,ICAM-1 and VCAM-1 were significantly decreased(P<0.05),and the concentration of IL-10 was significantly increased in serum(P<0.05).Overall,astragalosideⅣhas a good therapeutic effect on AR mice.It reduces the production of pro-inflammatory cytokines by inhibiting HMGB1/TLR4/NF-κB signaling pathway,which may be one of the important molecular mechanisms of the effectiveness of astragalosideⅣin the treatment of AR.
作者
田滢
张飞
段传新
TIAN Ying;ZHANG Fei;DUAN Chuan-xin(Department of Otolaryngology,Maternal and Child Health in Hubei Province,Wuhan 430069,China)
出处
《现代免疫学》
CAS
北大核心
2021年第1期50-55,共6页
Current Immunology