摘要
为探讨黄芪甲苷Ⅳ(astragalosideⅣ,ASTⅣ)对哮喘小鼠免疫失衡的调节机制,用卵清蛋白(ovalbumin,OVA)诱导小鼠支气管哮喘模型,随机分为对照组、模型组、ASTⅣ治疗组和地塞米松治疗组。HE染色观察肺组织病理改变;ELISA检测肺组织匀浆中IFN-γ、IL-5、IL-13、IL-17A及TGF-β的含量变化;RT-PCR检测脾脏中转录因子T-bet、GATA-3、STAT-6、RORγt和Foxp3 mRNA的表达水平。结果显示,ASTⅣ作用后小鼠肺部炎症细胞浸润及气道上皮细胞损伤明显改善;IL-5、IL-13和IL-17A的表达水平明显低于模型组(P<0.05),而对IFN-γ和TGF-β没有显著作用;ASTⅣ能显著抑制STAT-6 mRNA的表达(降低2.65倍),同时对GATA-3(降低1.82倍)和RORγt(降低2.22倍)的表达也有抑制作用;但对Foxp3和T-bet mRNA表达无显著影响。研究表明,ASTⅣ主要通过显著抑制Th2转录因子表达来抑制炎性因子IL-5、IL-13以及IL-17A的产生,从而改善哮喘模型小鼠肺部炎症程度。故ASTⅣ可能是一种哮喘治疗新的药物活性成分。
We aimed to explore the mechanisms of how ASTⅣsuppresses airway inflammation in bronchial asthma.Ovalbumin-induced mouse asthma model was established.A total of 40 BALB/c male mice were selected and divided into control,asthma,ASTⅣand dexamethasone groups.HE staining was conducted to observe the pulmonary pathological changes.ELISA was adopted for measuring the levels of IFN-γ,IL-5,IL-13,IL-17A and TGF-β,and RT-PCR for mRNA measurement of the main transcriptional factors T-bet,GATA-3,STAT6,RORγt and Foxp3.Compared with the control group,the asthma group had irregular tissue structure and severe inflammation.ASTⅣstrongly ameliorated injury of airway epithelial cells,diminished accumulation of inflammatory cells,and reduced levels of Th2 cytokines IL-5,IL-13 and IL-17A in the lung homogenate(P<0.05).But ASTⅣhad no significant effect on IFN-γand TGF-β.ASTⅣexerted immunomodulatory effects by suppressing production of Th2 cytokines IL-5 and IL-13 through downregulation of STAT-6 mRNA(2.65 folds)and GATA-3 mRNA(1.82 folds),meanwhile,ASTⅣalso suppressed expression of RORγt mRNA(2.22 folds),but had no effect on Tbet and Foxp3 mRNA.These results suggest that the anti-asthmatic activity of ASTⅣmay occur by the suppression of IL-5,IL-13 and IL-17A production through inhibition of the main transcriptional of factors of Th2 cell,resulting in the improvement of allergic asthma.ASTⅣcould be a new therapeutic component for allergic asthma.
作者
黄思捷
王嵩
郁兰
郤庆
李国文
沈朝斌
HUANG Si-jie;WANG Song;YU Lan;XI Qing;LI Guo-wen;SHEN Chao-bin(Department of Pharmacy,Shanghai TCM-Integrated Hospital,Shanghai University of TCM,Shanghai 200082,China;Department of Pediatrics,Shanghai TCM-Integrated Hospital,Shanghai University of TCM,Shanghai 200082,China;Department of Manufacture Planning,Zhonghua Pharmaceutical(Shanghai)Co.Ltd,Shanghai 201707,China)
出处
《现代免疫学》
CAS
CSCD
北大核心
2020年第1期28-33,共6页
Current Immunology
基金
上海市卫计委科研课题青年项目(20174Y0160)
上海市卫计委进一步加快中医药事业发展三年行动计划项目(ZY3-RCPY-3-1038)
上海市"医苑新星"青年医学人才培养资助计划(RCPY0020).
作者简介
黄思捷(1985-),女,工程师,主要从事中药新药研发与生产管理;通信作者:李国文(E-mail:lgwshutcm@163.com);通信作者:沈朝斌(Email:sbsys1303@aliyun.com)
