粉防己碱抑制支气管哮喘小鼠肺组织核因子-κB和诱导型一氧化氮合酶的研究  

Inhibition of airway inflammation and hyperresponsiveness by tetrandrine via downregulation of nuclear factor-κB and inducible nitric oxide synthase in asthmatic mice

作　　者：谢林艳[1] 陈子[1] 闫兆[1] 陆娇[1] 柏芳芳 马元[1] 黄茂[1] 周林福[1,2] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,210029 [2]江苏盛泽医院(江苏省人民医院盛泽分院)呼吸内科,苏州215228

出　　处：《国际呼吸杂志》2015年第9期641-646,共6页International Journal of Respiration

基　　金：国家自然科学基金（81370133、81170018）;江苏省医学重点人才项目（RC2011066）;江苏省333高层次人才培养工程（201115）;江苏省高校自然科学研究项目（11KJB320008）;江苏省高校优势学科建设工程（Jxl0231801）;江苏省临床医学科技专项（BL2012012）;苏州市科技计划项目（SYS201402）

摘　　要：目的探讨粉防己碱对支气管哮喘（简称哮喘）小鼠肺组织核因子-κB（NF-κB）、诱导型一氧化氮合酶（iNOS）表达、气道炎症和气道高反应性的影响。方法将32只SPF级BALB／c小鼠随机分为正常组、哮喘组、地塞米松组（激素组）和粉防己碱组（Tet组）。卵白蛋白（OVA）致敏和激发建立哮喘小鼠模型。末次激发24h后，肺功能仪测定小鼠气道阻力；HE染色观察气道炎症细胞浸润；ELISA检测血清总IgE、OVA特异性IgE（OVA-sIgE）及BALF中Th2细胞因子IL-4和IL-13水平；显微镜下计BALF中细胞总数，瑞氏染色计嗜酸粒细胞分类计数；Westernblot检测肺组织NF-κB和iNOS蛋白表达水平。结果与正常组比较，哮喘组气道阻力、气道炎症浸润、BALF炎症细胞总数和嗜酸粒细胞分类计数、血清总IgE和OVA—sIgE、BALF中IL-4和IL-13以及NF-κB和iNOS蛋白表达水平均显著增高（P〈0．05）；与哮喘组比较，激素和Tet干预组上述各项指标均显著降低（P〈0．05）。结论粉防己碱可下调哮喘小鼠肺组织NF--κB和iNOS表达并抑制气道炎症和气道高反应性。Objective To investigate the effect of tetrandrine （Tet） on the expression of nuclear factor-κB （NF-κB）,inducible nitric oxide synthase （iNOS）, airway inflammation and hyperresponsiveness in a murine model of bronchial asthma （asthma）. Methods Thirty-two SPF BALB/c mice were randomly divided into 4 groups,including control group, asthma group,dexamethasone group（glucocorticoid group） and atetrandrine group （Tet group）. Mice were sensitized and challenged by ovalbumin （OVA）. Twentyfour hours after the last challenge, airway resistance was measured by pulmonary function detector. Hematoxylin ＆ eosin （HE） staining was used to observe the airway inflammatory cells infiltration. Levels of total IgE and OVA-specific IgE （OVA-slgE） in serum and Th2 cytokines （IL-4 and IL-13） in bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. Total number of inflammatory cells in BALF were counted with a microscope. Smears of BALF cells were stained with Wright＇s staining for eosinophils differential count. The protein expression of NF-κB and iNOS were determined by western blot analysis. Results Compared to the control group, the airway resistance,airway eosinophilia, total inflammatory cells and differential eosinophils count in BALF, total IgE and OVA-sIgE in serum,Th2 cytokines （IL-4 and IL-13） in BALF,as well as the protein expression of NF-κB and iNOS were significantly increased in asthma group （ P 〈0.05）. In comparison with the asthma group, all the above indicators were remarkably decreased by treatment with either dexamethasone or tetrandrine （ P 〈 0.05 ）. Conclusions Tetrandrine may inhibit airway inflammation and hyperresponsiveness through downregulation of the expression of NF-κB and iNOS in asthmatic mice.

关 键 词：哮喘 粉防己碱 核因子-ΚB 诱导型一氧化氮合酶 

分 类 号：R285.5[医药卫生—中药学]