基于miR-146a/TLR4/NF-κB信号通路探讨辛前甘桔汤对慢性鼻窦炎大鼠的影响  

Effect of Xin-Qian-Gan-Jie decoction on chronic nasosinusitis in rats based on miR-146a/TLR4/NF-κB signaling pathway

作　　者：施陈燕 孙茹 滕磊[1] 蔡蔚然 董雪林 鞠晗 丁旭 暴喜明 张治军[1] 袁波[1] SHI Chenyan;SUN Ru;TENG Lei;CAI Weiran;DONG Xuelin;JU Han;DING Xu;BAO Ximing;ZHANG Zhijun;YUAN Bo(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203)

机构地区：[1]上海中医药大学附属曙光医院,上海201203

出　　处：《现代中西医结合杂志》2025年第4期439-444,472,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金资助项目(82174447,82104940)。

摘　　要：目的基于微小RNA-146a(miR-146a)/Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路探讨辛前甘桔汤治疗慢性鼻窦炎的作用机制。方法将24只雄性SD大鼠随机分成4组,每组6只。除正常组外,其余组大鼠用金黄色葡萄球菌制备慢性鼻窦炎模型。造模结束后,辛前甘桔汤组给予辛前甘桔汤水煎液0.6 g/kg灌胃,羧甲司坦组给予羧甲司坦口服液0.3 mL/kg灌胃,正常组和模型组给予生理盐水灌胃,均1次/d,连续灌胃14 d。HE和AB-PAS染色法观察鼻黏膜组织病理学形态,ELISA法检测鼻黏膜组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、黏蛋白5AC(MUC5AC)含量,qRT-PCR法检测鼻黏膜组织中TLR4、髓样分化因子88(Myd88)、白细胞介素-1受体相关激酶4(IRAK4)、肿瘤坏死因子受体相关因子6(TRAF6)、MUC5AC、miR-146a mRNA表达情况,Western blot法检测鼻黏膜组织中TLR4、NF-κB p-p65、MUC5AC蛋白表达情况。结果与正常组比较,模型组大鼠鼻黏膜上皮结构紊乱,纤毛脱落及粘连明显,杯状细胞增生,伴有大量炎性细胞浸润;鼻黏膜组织中IL-1β、IL-6、TNF-α、MUC5AC含量和鼻黏膜组织中TLR4、Myd88、TRAF6、MUC5AC mRNA相对表达量及TLR4、NF-κB p-p65、MUC5AC蛋白相对表达量均明显升高(P均<0.05),鼻黏膜组织中miR-146a mRNA相对表达量明显降低(P<0.05)。与模型组比较,辛前甘桔汤组与羧甲司坦组大鼠鼻黏膜上皮纤毛局部粘连,杯状细胞增生减轻;鼻黏膜组织中IL-1β、IL-6、TNF-α、MUC5AC含量和鼻黏膜组织中TLR4、Myd88、TRAF6、MUC5AC mRNA相对表达量及TLR4、NF-κB p-p65、MUC5AC蛋白相对表达量均明显降低(P均<0.05),鼻黏膜组织中miR-146a mRNA相对表达量均明显升高(P均<0.05)。4组大鼠鼻黏膜组织中IRAK4 mRNA相对表达量比较差异均无统计学意义(P均>0.05)。结论辛前甘桔汤能明显减轻慢性鼻窦炎大鼠鼻黏膜损伤,减少黏蛋白分泌,其作用机制可能与调节miR-146aObjective It is to explore the mechanism of action of Xin-Qian-Gan-Jie decoction in the treatment of chronic sinusitis in rats based on microRNA-146a(miR-146a)/toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB).Methods Twenty-four male SD rats were randomly divided into 4 groups,with 6 rats in each group.The rats of all groups except for the normal group were prepared with Staphylococcus aureus to establish models of chronic sinusitis.At the end of modeling,the Xin-Qian-Gan-Jie decoction group was given Xin-Qian-Gan-Jie decoction 0.6 g/kg by gavage,the carboxymethyl methacrylate group was given carboxymethyl methacrylate oral solution 0.3 mL/kg by gavage,the normal group and model group were given normal saline by gavage,all once daily,continuously treated for 14 days.The histopathological morphology of nasal mucosa was observed by HE and AB-PAS staining,the contents of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and mucin 5AC(MUC5AC)were detected by ELISA,the mRNA expressions of TLR4,myeloid differentiation factor 88(Myd88),interleukin-1 receptor-associated kinase 4(IRAK4),tumor necrosis factor receptor-associated factor 6(TRAF6),MUC5AC and miR-146a in nasal mucosa tissues were detected by qRT-PCR,and the protein expressions of TLR4,NF-κB p-p65 and MUC5AC in nasal mucosa tissues were detected by Western blot.Results Compared with the normal group,the nasal mucosal epithelial structure of rats in the model group was disordered,with significant cilia shedding and adhesion,goblet cell proliferation,and accompanied by a large amount of inflammatory cell infiltration;the contents of IL-1β,IL-6,TNF-αand MUC5AC,mRNA relative expressions of TLR4,Myd88,TRAF6 and MUC5AC,and protein relative expressions of TLR4,NF-κB p-p65 and MUC5AC in nasal mucosal tissue were significantly increased(all P<0.05),while the mRNA relative expression of miR-146a in nasal mucosal tissue was decreased(P<0.05).Compared with the model group,the nasal mucosal epithelial cilia in the Xin-Qian-Gan-Jie decocti

关 键 词：慢性鼻窦炎 辛前甘桔汤 微小RNA-146a TOLL样受体4 核因子-ΚB 

分 类 号：R-332[医药卫生]