JunB在实验性支气管哮喘中的作用  

Role of JunB in experimental bronchial asthma

作　　者：李海燕[1] 郭琦[2] 陈如冲[3] 周一平[2] 李明[2] 喻海琼[2] 江梅[3] 

机构地区：[1]广东医学院附属福田医院社康部,广东深圳518033 [2]广东医学院附属福田医院呼吸科,广东深圳518033 [3]广州呼吸疾病研究所(呼吸疾病国家重点实验室),广东广州510120

出　　处：《海南医学》2013年第6期781-784,共4页Hainan Medical Journal

基　　金：广东省医学科学技术研究基金(编号:A2009621);深圳市科技计划重点项目(编号:200901023);福田区公益性科研项目(编号:FTWS201040)

摘　　要：目的探索激活蛋白-1(Activator protein-1,AP-1)家族成员中参与构成哮喘病理生理特征的关键亚单位,为哮喘治疗提供更精确和新颖分子靶点。方法建立大鼠哮喘模型。130只雄性Wistar大鼠随机分为正常对照组、哮喘空白组、c-Jun反义寡核苷酸(Antisense oligodeoxynucleotides,AS-ODNs)组、JunB AS-ODNs组、JunD AS-ODNs组、c-FosAS-ODNs组、FosBAS-ODNs组、Fra-1 AS-ODNs组、Fra-2 AS-ODNs组和无义寡核苷酸(Nonsense ODNs,NS-ODNs)组。实施基因沉默后,HE染色计数支气管肺泡灌洗液中嗜酸粒细胞(Eosinophils,EOS)百分比,逆转录-聚合酶链反应检测白介素(Interleukin,IL)-5mRNA表达。结果 JunBAS-ODNs组的EOS百分比[(13.39±3.72)%]显著低于哮喘空白组[(34.33±9.62)%],差异有统计学意义(P<0.001),但仍高于正常对照组[(5.61±1.76)%],差异有统计学意义(P<0.05)。其余ODNs组的EOS百分比与哮喘空白组的差异均无统计学意义(P>0.05)。与哮喘空白组比较,JunB AS-ODNs组的IL-5 mRNA表达被显著抑制[(0.5542±0.0829)vs(0.8224±0.0660),P<0.001],但亦仍高于正常对照组[(0.3237±0.0577),P<0.001]。其余ODNs组IL-5 mRNAs表达与哮喘空白组比较,差异均无统计学意义(P>0.05)。结论在转录因子AP-1家族中,JunB亚单位可能决定哮喘大鼠气道慢性炎症,可能是新颖治疗靶点。Objective To determine the key activator protein-1（AP-1） subunit involved in the characteristics of the pathophysiology of asthma,in order to provide more accurate and novel molecular targets for the treatment of asthma.Methods Asthmatic rat models were employed.One hundred and thirty Wistar male rats were randomly divided into normal control,blank control,c-Jun antisense oligodeoxynucleotides（AS-ODNs）,JunB AS-ODNs,JunD AS-ODNs,c-Fos AS-ODNs,FosB AS-ODNs,Fra-1 AS-ODNs,Fra-2 AS-ODNs,and nonsense ODNs groups.After gene silencing,the percentages of eosinophils（EOS） in the bronchoalveolar lavage fluid were calculated using haematoxylin-eosin staining,and interleukin（IL）-5 mRNA was detected by reverse transcription-polymerase chain reaction（RT-PCR）.Results The percentage of EOS in JunB AS-ODNs group was decreased significantly as compared with that in the blank control [（34.33±9.62）% vs（13.39±3.72）%,P0.001],but was still higher than that in the normal control [（5.61±1.76）%,P=0.04].No significant differences in the percentages of EOS between other ODNs groups and the blank control were observed（P0.05）.Compared with that in the blank control,the expression of IL-5 mRNA in JunB AS-ODNs group was markedly suppressed [（0.554 2 ± 0.082 9） vs（0.822 4 ± 0.066 0）,P0.001],which was also still higher than that in the normal control [（0.323 7±0.057 7）,P0.001].There were no significant differences in the expression of IL-5 mRNA between other ODNs groups and the blank control（P0.05）.Conclusion Chronic airway inflammation in asthmatic rats might depend on JunB,one of the subunits in the family of transcription factor AP-1.JunB might be a novel therapeutic target in asthma.

关 键 词：激活蛋白-1 亚单位 反义寡核苷酸 支气管哮喘 

分 类 号：R562.22[医药卫生—呼吸系统]