Pyrin重组蛋白通过TGF-β1/SMAD及Jagged1/Notch1信号通路减轻慢性支气管哮喘小鼠气道炎症及气道重塑  

Recombinant pyrin domain protein attenuates airway inflammation and airway remodeling through TGF-β1/SMAD and Jagged1/Notch1 signaling pathways in chronic bronchial asthma mice

作　　者：王知广 姜京植[2] 王重阳 李俊峰 徐畅[2] 延光海[2] 朴艺花[3] 朴红梅[1] WANG Zhiguang;JIANG Jingzhi;WANG Chongyang;LI Junfeng;XU Chang;YAN Guanghai;PIAO Yihua;PIAO Hongmei(Department of Respiratory Medicine,Hospital of Yanbian University,Yanji 133000;Department of Anatomy,College of Medicine,Yanbian University,Yanji 133002;Department of Critical Care Medicine,Hospital of Yanbian University,Yanji 133000,China)

机构地区：[1]延边大学附属医院呼吸内科,吉林延吉133000 [2]延边大学解剖学教研室,吉林延吉133002 [3]延边大学附属医院重症医学科,吉林延吉133000

出　　处：《细胞与分子免疫学杂志》2020年第3期220-227,共8页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81660003)。

摘　　要：目的探讨pyrin重组蛋白是否通过抑制转化生长因子β1(TGF-β1)/SMAD及Jagged1/Notch1信号通路缓解卵清蛋白(OVA)诱导的慢性哮喘小鼠气道炎症及气道重塑。方法选取雄性BALB/c小鼠32只,分为4组,每组8只。分别为对照组、OVA模型组、pyrin重组蛋白治疗组(100μg/kg)、地塞米松(DEX)治疗组(1 mg/kg)。ELISA测定各组小鼠肺泡灌洗液(BALF)中炎症因子的表达,HE染色观察小鼠支气管炎症浸润情况,过碘酸雪夫反应(PAS)染色观察杯状细胞数量变化,Masson染色观察胶原纤维沉积,免疫组织化学染色法观察α平滑肌肌动蛋白(α-SMA)、TGF-β1和Notch1蛋白在肺组织中表达分布情况,Western blot法检测肺组织中α-SMA、上皮钙黏素(E-cadherin)、TGF-β1、SMAD2/3、SMAD7、Jagged1、Notch1、Hes1蛋白水平。结果Pyrin重组蛋白能够改善OVA诱导的支气管哮喘小鼠气道炎症反应,抑制杯状细胞的增生及胶原纤维沉积,降低BALF中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-4、IL-13含量,抑制肺组织中TGF-β1、SMAD2/3、Jagged1、Notch1、Hes1、α-SMA的蛋白表达。结论Pyrin重组蛋白通过下调TGF-β1/SMAD及Jagged1/Notch1信号通路减轻哮喘小鼠气道炎症及气道重塑。Objective To investigate whether the recombinant pyrin domain protein can alleviate the airway inflammation and airway remodeling of OVA-induced mice with chronic asthma by inhibiting transforming growth factorβ1(TGF-β1)/SMAD and Jagged1/Notch1 signaling pathways.Methods Thirty-two male BALB/c mice were selected and divided into 4 groups with 8 mice in each group.The four groups were the control group,OVA model group,recombinant pyrin domain protein treatment group(100μg/kg),and the dexamethasone treatment group(1 mg/kg).Enzyme-linked immunosorbent assay(ELISA)was used to determine the expression of inflammatory factors in bronchoalveolar lavage fluid(BALF)of mice in each group.hematoxylin-eosin staining(HE)was used to observe the inflammatory infiltration of bronchus in mice.The changes of goblet cells were observed by periodic acid-Schiff(PAS)staining and collagen fibers by Masson staining.Immunohistochemical staining(IHC)was performed to observe the expression distribution ofαsmooth muscle actin(α-SMA),TGF-β1 and Notch1 proteins in lung tissues.Western blotting was used to detect the protein levels ofα-SMA,E-cadherin,TGF-β1,SMAD2/3,SMAD7,Jagged1,Notch1 and Hes1 in lung tissues.Results The recombinant pyrin domain protein not only improved the airway inflammatory response of the OVA-induced mice with bronchial asthma,but also inhibited the hyperplasia of goblet cells and collagen fiber deposition,reduced the tumor necrosis factorα(TNF-α)in BALF,interleukin 1β(IL-1β),IL-4,IL-13 levels,and inhibited the protein expression of TGF-β1,SMAD2/3,Jagged1,Notch1,Hes1 andα-SMA in lung tissues.Conclusion The recombinant pyrin domain protein can reduce the airway inflammation and airway remodeling of asthmatic mice by inhibiting TGF-β1/SMAD and Jagged1/Notch1 signaling pathways.

关 键 词：Pyrin重组蛋白 支气管哮喘 气道炎症 气道重塑 转化生长因子β1(TGF-β1) NOTCH1 

分 类 号：R562.25[医药卫生—呼吸系统] R364.5[医药卫生—内科学]