木兰脂素调控Fyn-STAT5通路治疗变应性鼻炎  

Study on Magnolian in the Treatment of Allergic Rhinitis by Regulating the Fyn-STAT5 Pathway

作　　者：张晓芳[1] 刘慧娜[1] ZHANG Xiao-fang;LIU Hui-na(Zhengzhou Orthopedics Hospital,Zhengzhou,Henan,China,450052)

机构地区：[1]郑州市骨科医院,河南郑州450052

出　　处：《河南中医》2023年第6期864-871,共8页Henan Traditional Chinese Medicine

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20191139)。

摘　　要：目的:探讨木兰脂素调控致密物酪氨酸激酶(dense tyrosine kinase Fyn, Fyn)/信号转导和转录激活因子5(signal transducers and activators of transduction 5,STAT5)通路治疗变应性鼻炎(allergic rhinitis, AR)的效果。方法:将58只豚鼠采用随机数字表法分为建模组(n=50)、空白组(n=8)。建模组采用卵清白蛋白抗原混悬液全身及局部攻击建立AR模型,将建模成功的豚鼠随机分为模型组、氯雷他定组(1.05 mg·kg^(-1))及木兰脂素低剂量组(20 mg·kg^(-1))、木兰脂素中剂量组(40 mg·kg^(-1))、木兰脂素高剂量组(80 mg·kg^(-1))。给予相应药物灌胃干预,模型组和空白组以等体积生理盐水灌胃,灌胃体积为10 mL·kg^(-1),每天1次,连续7 d。对比干预前后各组豚鼠鼻部症状评分;HE染色观察各组豚鼠鼻黏膜组织病理变化。体外分离并鉴定各组豚鼠鼻黏膜成纤维细胞,转化生长因子-β1干预各组成纤维细胞后采用Western Blot检测Fyn、STAT5、干细胞因子(stem cell factor, SCF)、白细胞介素-10(interleukin-10,IL-10)蛋白表达水平;RT-qPCR检测Fyn mRNA、STAT5 mRNA、SCF mRNA、IL-10 mRNA表达水平。结果:与模型组比较,木兰脂素各剂量组豚鼠鼻部症状评分显著降低(P<0.05),鼻黏膜病理变化明显减轻。各组鼻黏膜成纤维细胞中波形蛋白均呈强阳性表达,提示鼻黏膜成纤维细胞成功分离;与模型组比较,木兰脂素各剂量组Fyn、SCF蛋白与mRNA表达水平明显降低(P<0.05),STAT5、IL-10蛋白与mRNA表达水平明显升高(P<0.05),且呈剂量依赖性。结论:木兰脂素可减轻AR豚鼠的鼻部症状和鼻黏膜组织病理改变,其作用机制可能与调控Fyn-STAT5通路进而调节免疫反应有关。Objective: To investigate the efficacy of magnolian in regulating dense tyrosine kinase(Fyn)/signal transducers and activators of transcription 5(STAT5) pathway in the treatment of allergic rhinitis(AR).Methods: A total of 58 guinea pigs were randomly divided into a modeling group(n=50) and a blank group(n=8) by using a random number table method.The modeling group established an AR model by using whole body and local attack with egg albumin antigen suspension.The successfully modeled guinea pigs were randomly divided into the model group, the loratadine group(1.05 mg·kg^(-1)),and the magnolian low-dose group(20 mg·kg^(-1)),the medium-dose group(40 mg·kg^(-1)),and the high-dose group(80 mg·kg^(-1)).Corresponding medication was administered by gavage for intervention.The model group and the blank group were gavaged with equal volume of physiological saline, with a gavage volume of 10 mL·kg^(-1),once a day, for 7 consecutive days.The nasal symptom scores of each group before and after intervention were compared.HE staining was used to observe the pathological changes of nasal mucosa tissue.Fibroblasts from the nasal mucosa of guinea pigs in each group were isolated and identified in vitro.After transforming growth factors-β intervened various constituent fibroblasts, Western blot was used to detect the expression levels of Fyn, STAT5,stem cell factor(SCF),and interleukin-10(IL-10) proteins;RT qPCR was used to detect the expression levels of Fyn mRNA,STAT5 mRNA,SCF mRNA,and IL-10 mRNA.Results: Compared with the model group, the nasal symptom scores of guinea pigs in each dose group of magnolian significantly decreased(P<0.05),and the pathological changes of the nasal mucosa were significantly alleviated.The strong positive expression of Vimentin in nasal mucosa fibroblasts in each group suggested that nasal mucosa fibroblasts were successfully isolated.Compared with the model group, the expression levels of Fyn, SCF protein, and mRNA in each dose group of magnolian were significantly reduced(P<0.05),while the

关 键 词：木兰脂素 变应性鼻炎 鼻黏膜成纤维细胞 Fyn-STAT5通路 豚鼠 

分 类 号：R285.5[医药卫生—中药学]