CpG ODN对小鼠哮喘模型气道炎症及信号转导子和转录激活子6(STAT6)表达的影响  

CpG ODN attenuates airway inflammation and modulates the expression of signal transducers and activators of transcription 6 in asthmatic mice

作　　者：杨远[1] 彭小华[2] 林勇[1] 

机构地区：[1]东南大学附属中大医院呼吸内科 [2]山西省长治市妇幼保健院

出　　处：《中国临床药理学与治疗学》2010年第2期149-153,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:研究寡核甘酸免疫刺激序列(CpGoligonucleotides,CpG ODN)对急性支气管哮喘小鼠气道炎症及信号转导子和转录激活子6(STAT6)表达的调控作用。方法:将32只雄性BALB/c小鼠随机分为对照组、哮喘组、地塞米松干预组和CpG ODN干预组,建立急性哮喘气道炎症模型。对支气管肺泡灌洗液(BALF)进行细胞总数、嗜酸粒细胞(EOS)分类计数;取左叶肺组织切片做HE染色观察气道和肺组织炎症改变;用免疫组织化学法检测气道上皮组织中STAT6表达。结果:哮喘组小鼠BALF中细胞总数、EOS绝对值显著高于对照组(P<0.05),地塞米松组和CpG ODN组上述炎症细胞计数比哮喘组明显减少(P<0.05)。HE染色示地塞米松组和CpG ODN组小鼠肺组织炎症程度较哮喘组减轻。STAT6在气道上皮细胞表达,哮喘组气道上皮细胞中STAT6表达较对照组增强,地塞米松组和CpG ODN组STAT6表达与哮喘组比较有明显减少(P<0.05),较对照组增加。支气管上皮细胞STAT6蛋白表达与BALF中的EOS绝对值呈显著正相关(r=0.748),而地塞米松组和CpG ODN组之间的作用无统计学差异(P>0.05)。结论:应用地塞米松和CpG ODN均可在一定程度上减轻哮喘小鼠的气道炎症,CpGODN可能通过下调肺组织中STAT6蛋白的过度表达,从而抑制依赖于STAT6/IL-4通路的急性气道炎症,减轻哮喘的症状。AIM： To investigate the effects of CpG ODN on the airway inflammation and the expression of signal transducers and activators of transcription 6（STAT6） in asthma. METHODS： Thirty-two male BALB/c mice were randomly divided into 4 equal groups., control group,asthma group, DXM group and CpG ODN group , the mice model of asthma was established by the ovalbumin（OVA） challenge methods. The lung tissue was gained from the left lung, bronchoal- veolar lavage fluid （BALF） was obtained from the right lung. The total cell numbers, eosinophils（EOS） numbers in BALF were counted by different count fluids; Left lung tissue was stained by HE and the changes of inflammation were observed. The protein expressions of STAT6 were detected by immunohistochemistry. RESULTS： The total cell numbers in BALF, the absolute numbers of EOS were all significantly higher in asthma group than those in the control group（P〈0.05）; the total cell numbers in BALF, the absolute numbers of EOS were all significantly lower in DXM group and CpG ODN group than those in asthma group（P CpG ODN and DXM attenuated the airway inflammation of asthmatic mice. The ex- pressions of STAT6 were mainly on the bronchial epithelium. STAT6 protein levels were increased in asthma group. CpG ODN significantly reduced STAT6 protein expression. DXM sig nificantly reduced the levels of STAT6 protein. There was a significant positive correlation between the absolute numbers of EOS in BALF, the content of STAT6 in the epithelial cells（r= 0. 748）. CONCLUSION： CpG ODN and DXM can extenuate the progression of airway inflammation following down regulated allergen challenge via regulation of STAT6/IL- 4 signal pathway.

关 键 词：支气管哮喘 非甲基化胞嘧啶-乌嘌呤寡核苷酸 信号转导子和转录激活子6 地塞米松 

分 类 号：R562.2[医药卫生—呼吸系统]