摘要
目的探讨支气管哮喘(简称哮喘)急性发作期激活转录因子-3(ATF3)的表达及作用。方法 30只健康雄性豚鼠,按随机数字表法分为对照组(A组)、哮喘组(B组)及地塞米松治疗组(C组),每组10只。卵清蛋白致敏法复制哮喘模型。收集支气管肺泡灌洗液(BALF)并进行细胞总数及分类计数;观察豚鼠肺组织病理学改变;检测豚鼠肺组织及BALF中ROS含量;采用免疫组织化学和Westernblot法测定豚鼠肺组织中ATF3蛋白的表达和量的变化;原位杂交、RT-PCR法检测ATF3 mRNA的表达变化;免疫细胞化学检测豚鼠BALF细胞中ATF3蛋白的表达。结果①哮喘组豚鼠BALF中炎细胞总数、嗜酸粒细胞百分比(EOS%)显著高于对照组(P<0.01),哮喘组豚鼠肺组织可见大量炎症细胞浸润及明显气道重塑改变,且哮喘组ROS含量显著升高,而地塞米松治疗组上述变化明显减低(P值均<0.01);②ATF3蛋白及mRNA表达哮喘组明显高于对照组(P值均<0.01);③ATF3蛋白及mRNA的表达变化与ROS含量及BALF炎细胞总数、EOS%变化均呈正相关。结论哮喘急性发作期豚鼠肺组织及BALF细胞中ATF3的表达升高,可能与气道炎症反应和氧化应激有关;给予地塞米松治疗后ATF3表达下降,可能在哮喘的防治中起重要作用。
Objective To investigate the effect of ATF3 expression in acute exacerbation of bronchial asthma（asthma）.Methods Thirty healthy male guinea pigs were randomly divided into 3 groups：the control group（group A）,asthmatic group（group B）,Dexamethasone group（group C）,10 guinea pigs in each group.The asthmatic model was established by the ovalbumin challenge method.Collected BALF of guinea pigs in each group and determed the total number of BALF cells and cells classification,and the changes in lung histopathology were observed.Tested the content of reactive oxygen species（ROS） in lung tissue,BALF of guinea pigs.In the lung tissue of guinea pigs,the ATF3 protein was detected by immunohischemistry,Western blot,and ATF3 mRNA was tested by in situ hybridization,RT-PCR.The expression of ATF3 protein in BALF cells was observed immunocytochemistry.Results ①The total number of inflammatory cells and EOS% in BALF of asthma group were significantly higher than those of control group（P0.01）,and large numbers of inflammatory cell infiltration and obviously bronchiole remodeling response could be seen in this group,high lever of ROS also could be detected in the lung tissue and BALF of asthma group.However,all these changes were obvious ameliorated after treatment with Dexamethasone.② Protein and mRNA expressions of ATF3 in asthma group were significantly higher than those in control group（P0.01）.③ Linear correlation analysis showed that changes of ATF3 mRNA and protein expression were positive correlated with the contents of ROS,and the total number of inflammatory cells,EOS% in BALF.Conclusions The expression of ATF3 was increased in the lung tissue and BALF cells from asthma guinea pigs during acute exacerbation,which may be related to airway inflammation and oxidative stress.After treatment with dexamethasone,the expression of ATF3 was decreased,suggested that maybe ATF3 played important role in the prevention and cure of asthma.
出处
《中华哮喘杂志（电子版）》
CAS
2011年第4期5-9,共5页
Chinese Journal of Asthma(Electronic Version)
基金
湖南省卫生厅科研计划课题项目(B2010-089
B2007169)
湖南省科技计划项目(2010FJ6113)
湖南省自然科学基金(09JJ5021)
关键词
支气管哮喘
激活转录因子3
氧化应激
Bronchial asthma Activating transcription factor 3 Oxidative stress
