通窍平喘方调节TLR4/MyD88/NF-кB通路及免疫平衡改善过敏性鼻炎-哮喘综合征小鼠炎症反应OA
Tongqiao Pingchuan Formula(通窍平喘方)to ameliorate inflammatory responses in the model mice of combined allergic rhinitis and asthma syndrome by modulating the TLR4/MyD88/NF-κB signaling pathway and immune balance
目的 探究通窍平喘方对小鼠过敏性鼻炎-哮喘综合征(CARAS)的影响及潜在机制.方法 36只小鼠随机分为空白对照组、模型对照组、阳性对照地塞米松组(1.5 mg·kg-1·d-1)、通窍平喘方低、中、高剂量组(5.85、11.7、23.4 g·kg-1·d-1)每组6只.除外空白组,其他小鼠均需建立OVA/AL(OH)3诱导的CARAS模型,并按照上述设定的剂量对各组小鼠进行药物干预.观察各组小鼠行为学特征;HE染色、PAS染色观察小鼠鼻黏膜、肺组织的病理学形态变化;ELISA检测小鼠肺泡灌洗液(BALF)及鼻腔灌洗液(NALF)中 IL-4、IL-13、IFN-γ、IL-6、TNF-α 水 平;RT-qPCR 检测 TLR4、Myd88、NF-κB、T-bet、GATA3 mRNA表达水平;Western blot检测肺组织中TLR4、MyD88、NF-кB、T-bet、GATA3蛋白表达水平.结果 与空白组相比,模型组小鼠行为学评分增高,鼻黏膜、肺组织可见结构改变、炎性细胞浸润、杯状细胞增生;BALF及NALF中IL-4、IL-13、IL-6、TNF-α增高,IFN-γ降低;鼻黏膜及肺组织中TLR4、MyD88、NF-кB、GATA3 mRNA和蛋白表达水平增高,T-bet降低.与模型组相比,通窍平喘方给药可显著降低行为学评分;改善小鼠鼻黏膜及肺组织的病理改变;减少BALF及NALF中IL-4、IL-13、IL-6、TNF-α并提升IFN-γ水平;减少鼻黏膜及肺组织中TLR4、MyD88、NF-кB、GATA3并提高T-bet的mRNA及蛋白表达.结论 通窍平喘方可抑制CARAS小鼠模型的变态反应性炎症反应,其机制可能与抑制TLR4/MyD88/NF-кB信号通路及调节Th1/Th2免疫平衡相关.
Objective To explore the effects and potential mechanisms of Tongqiao Pingchuan Formula(通窍平喘方,TQPCF)on a mouse model of combined allergic rhinitis and asthma syndrome(CARAS).Methods Thirty-six mice were randomly divided into the blank control,model control,positive control(dexamethasone,1.5 mg/kg/day),and TQPCF low/medium/high-dose groups(5.85,11.7,23.4 g/kg/day).Except for the blank group,mice were sensitized and challenged with OVA/Al(OH)3 to establish CARAS and then administered respective treatments.Observe the behavioral characteristics of each group of mice.Pathological changes in nasal mucosa and lung tissue were observed using HE and PAS staining.Levels of IL-4,IL-13,IFN-γ,IL-6,and TNF-α in bronchoalveolar lavage fluid(BALF)and nasal lavage fluid(NALF)were measured by ELISA.RT-qPCR detected mRNA levels of TLR4,MyD88,NF-κB p65,T-bet,and GATA3 in nasal mucosa and lung tissue.Western blot(WB)was used to assess protein levels of these targets in lung tissue.Results Model group mice showed an increase in behavioral scores,along with exhibited structural disruption,inflammatory cell infiltration,and goblet cell hyperplasia in nasal mucosa and lungs.In BALF and NALF,IL-4,IL-13,IL-6,and TNF-α levels were elevated,while IFN-γ was reduced.In nasal mucosa and lung tissue,TLR4,MyD88,NF-κB p65,and GATA3 mRNA expres-sions were increased,whereas T-bet mRNA was decreased.Similarly,TLR4,MyD88,NF-κB p65,and GATA3 protein levels in lung tissue were increased,and T-bet protein was decreased.Compared to the model group,TQPCF administration reduced the behavioral score,ameliorated pathological damage in nasal mucosa and lungs,decreased IL-4,IL-13,IL-6,and TNF-α levels in BALF and NALF,increased IFN-γ levels,and modulated the expression of TLR4,MyD88,NF-κB p65,GATA3,and T-bet at both mRNA and protein levels in nasal mucosa and lung tissue.Conclusion TQPCF alleviates allergic inflammatory responses in CARAS mice,poten-tially by inhibiting the TLR4/MyD88/NF-κB pathway and modulating Th1/Th2 immune balance.
王追越;刘亚尊;薛辉;薛征
上海中医药大学附属市中医医院,上海 200071||上海中医药大学,上海 201203上海中医药大学附属市中医医院,上海 200071上海中医药大学,上海 201203上海中医药大学附属市中医医院,上海 200071||上海中医药大学,上海 201203
医药卫生
通窍平喘方TLR4/MyD88/NF-кB免疫平衡过敏性鼻炎-哮喘综合征
Tongqiao Pingchuan Formula(通窍平喘方)TLR4/MyD88/NF-κBImmune balanceCombined allergic rhinitis and asthma syndrome
《时珍国医国药》 2026 (16)
3038-3045,8
国家自然科学基金面上项目(82274576)国家重点研发计划(2024YFC35059032024YFC3505900)上海市2022年度"科技创新行动计划"医学创新研究专项项目(22Y21920400)
评论