STAT6圈套寡核苷酸对支气管哮喘小鼠Eotaxin表达及气道炎症的抑制作用  

Inhibitory effects of STAT6 decoy oligonucleotides on Eotaxin expression and airway inflammation in mouse models of asthma

作　　者：周雨[1] 秦碧媛[1] 熊瑛[1] 

机构地区：[1]四川省泸州医学院附属医院呼吸内科,646000

出　　处：《重庆医学》2011年第28期2809-2811,2814,F0002,共5页Chongqing medicine

摘　　要：目的观察STAT6圈套寡核苷酸(ODN)对支气管哮喘小鼠嗜酸性粒细胞趋化因子(Eotaxin)表达及气道炎症的影响,探讨STAT6圈套ODN治疗支气管哮喘的可行性。方法将BALB-C雌性小鼠随机分为:健康对照组(N组)、哮喘组(A组)、STAT6圈套ODN哮喘组(ST-ODN组)及无序ODN哮喘组(SC-ODN组),ODN经鼻气道滴入ST-ODN组及SC-ODN组小鼠肺部,荧光显微镜观察肺组织中异硫氰酸荧光素标记的寡核苷酸(FITC-ODN)的分布;测定肺泡灌洗液(BALF)中白细胞(WBC)、淋巴细胞(LYM)及嗜酸性粒细胞(EOS)数量;观察气道炎症病理变化;免疫组化法检测肺组织Eotaxin蛋白;RT-PCR法检测肺组织Eotaxin mRNA表达。结果 (1)FITC-ODN转染组小鼠肺部发现FITC着色,ODN肺组织转染成功。(2)小鼠肺组织ST-ODN组较哮喘组炎症病理反应明显减轻。(3)BALF中哮喘组与空白对照组比较,WBC、LYM、EOS均增高,差异有统计学意义(P<0.01);ST-ODN组则明显低于哮喘组,差异有统计学意义(P<0.01);而SC-ODN组与哮喘组比较差异无统计学意义(P>0.05);(4)Eotaxin蛋白及mRNA表达:哮喘组明显高于空白对照组,差异有统计学意义(P<0.01);ST-ODN组低于哮喘组,差异有统计学意义(P<0.01);而SC-ODN组与哮喘组比较,差异无统计学意义(P>0.05)。结论 STAT6圈套ODN可经鼻气道滴入方式直接转染至小鼠肺组织;STAT6圈套ODN可抑制Eotaxin的表达,调控哮喘小鼠气道的EOS聚集;抑制哮喘小鼠气道炎症反应。Objective To observe the influence of STAT6 decoy Oligonucleotides on the Eotaxin expression and airway inflammation in mouse models of asthma.Methods BALB-C female mice were randomly divided into four groups：normal control（N）,asthma model（A）,asthma model administered by STAT6 decoy Oligonucleotides（ST-ODN）,and asthma model administered by scrambled Oligonucleotides（SC-ODN）.The STAT6 decoy ODN and scrambled ODN were intranasally administered respectively.The distribution of FITC-ODN in lungs were directly observed by fluorescence microscope.The numbers of white blood cells,lymphocytes and eosinophils in branehoalveolar lavage fluid were classified and measured by microscope.The pathological changes of airway inflammation were observed in lungs section.The mRNA and protein of Eotaxin expression in airway epithelium were detected by reverse transcription polymerase chain reactin（RT-PCR）and immunohistochemistry respectively.Results（1）We successfully observe green fluorescence in the lung tissue with FITC-ODN by local intranasal administration,demonstrating the efficacy of gene transfer into the lung.（2）Pathological changes of airway inflammation of asthma group significantly increased compared with that of the ST-ODN group.（3）In the BALF,the numbers of white blood cells/lymphocytes/eosinophils of asthma group significantly increased compared with those of normal control group（P0.01）.Those of T-ODN group were significantly lower than those of the asthma group（P0.01）,while there were no significant differences（P0.05）between the SC-ODN group and asthma group.（4）The protein and the mRNA expression of Eotaxin：those of asthma group significantly increased compared with those of normal group（P0.01）,and those of ST-ODN group were significantly lower than those of the asthma group（P0.01）,while there were no significant differences（P0.05）between the SC-ODN group and asthma group.Conclusion STAT6 decoy ODN can transfer into lung tissues of mice by local intranasal

关 键 词：转录激活因子类 寡核苷酸类 哮喘 趋化因子CCL11 趋化因子CCL24 

分 类 号：R562.25[医药卫生—呼吸系统]