转录因子ATF3和ATF4在大鼠慢性阻塞性肺疾病中的表达及作用  

Expressions and Roles of Activating Transcription Factor 3 and 4 in Rats with Chronic Obstructive Pulmonary Disease

作　　者：刘晓燕[1,2] 戴爱国 李洁 

机构地区：[1]南华大学研究生院,湖南衡阳421001 [2]湖南省老年医院老年医学研究所呼吸疾病研究室,湖南长沙410016

出　　处：《中国呼吸与危重监护杂志》2011年第2期121-125,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：湖南省科技计划重点项目(编号:2007FJ3016;2008FJ4206);湖南省医药卫生科研课题(编号:B2005125)

摘　　要：目的研究活化转录因子3(ATF3)和活化转录因子4(ATF4)在慢性阻塞性肺疾病(COPD)大鼠肺组织中的定位和表达,探讨其在COPD发病中的可能作用及意义。方法采用气管内注入脂多糖和熏香烟的方法复制大鼠COPD模型。观察COPD大鼠和正常对照组大鼠肺组织病理学改变,检测肺功能;应用原位杂交、逆转录-聚合酶链反应(RT-PCR)、免疫组化、Western blot检测大鼠肺组织中ATF3、ATF4 mRNA及蛋白的表达情况。结果 COPD组的肺功能指标(FEV0.3、FEV0.3/FVC、PEF)明显降低,光镜下肺组织病理改变符合COPD的特征性改变。免疫组化及Westernblot显示COPD组ATF3、ATF4蛋白水平较对照组升高(P<0.05);原位杂交及RT-PCR结果显示ATF3、ATF4 mRNA表达水平在COPD组显著高于对照组(P<0.05)。结论 COPD大鼠肺组织ATF3、ATF4表达明显上调,ATF3、ATF4可能参与调控COPD的氧化/抗氧化失衡。Objective To investigate the expression and localization of activating transcription factor 3(ATF3) and ATF4 in lung of rats with chronic obstructive pulmonary disease(COPD),and explore their possible roles in the pathogenesis of COPD.Methods Twenty-two SD rats were randomly divided into a COPD group and a control group.The COPD model was established by cigarette smoking and intratracheal instillation of lipopolysaccharide.The lung function was measured and the pathological changes were observed under light microscope.In situ hybridization,reverse transcription-polymerase chain reaction(RT-PCR),immunohistochemistry,and Western blot techniques were used to detect the mRNA and protein expressions of ATF3 and ATF4 in rat lung.Results The lung function of the COPD group was significantly decreased.The rats in the COPD group shared specific pathological features of COPD.Immunohistochemical and Western blot results showed that the protein expressions of ATF3 and ATF4 were higher in the COPD group than those in the control group(P<0.05).In situ hybridization and RT-PCR results showed that the mRNA expressions of ATF3 and ATF4 in the COPD group were also significantly higher than those in the control group(P<0.05).Conclusions The expressions of ATF3 and ATF4 are significantly up-regulated in COPD.These findings suggest that ATF3 and ATF4 may play important roles in the oxidative and antioxidative imbalance in the pathogenesis of COPD.

关 键 词：慢性阻塞性肺疾病 活化转录因子3 活化转录因子4 

分 类 号：R563.9[医药卫生—呼吸系统]