慢性阻塞性肺疾病的炎症反应与Foxp3、T-bet、GATA3表达失衡有关  

Imbalance in the expression of Foxp3,T-bet and GATA-3 is correlated with inflammation of chronic obstructive pulmonary disease

作　　者：王成阳[1,2] 刘向国[2] 彭青和[2] 李达[2] 季乔雪[2] 王传博[3] 李泽庚[4] 

机构地区：[1]湖北中医药大学研究生院,湖北武汉430065 [2]安徽中医药大学中西医结合临床学院,安徽合肥230038 [3]安徽医科大学第二附属医院中医科,安徽合肥230601 [4]安徽中医药大学第一附属医院呼吸科,安徽合肥230031

出　　处：《细胞与分子免疫学杂志》2014年第7期704-707,712,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81072781)

摘　　要：目的观察慢性阻塞性肺疾病(COPD)大鼠调节性T细胞(Treg)、叉头状转录因子3(Foxp3)、T-bet、GATA连接蛋白3(GATA3)的变化。方法将30只大鼠随机分为对照组、模型组,每组15只。模型组大鼠采用烟熏加脂多糖(LPS)气管滴入方法建立COPD模型。模型复制成功第28天,采用ELISA检测大鼠血清、支气管肺泡灌洗液(BALF)白介素4(IL-4)、γ干扰素(IFN-γ)水平,流式细胞术检测外周血Treg表达,分别采用逆转录PCR及Western blot法检测肺组织Foxp3、T-bet、GATA3mRNA和蛋白表达。结果模型组大鼠肺泡腔及肺间质内大量炎性细胞浸润,肺组织结构破坏。与对照组比较,模型组大鼠血清IFN-γ表达升高(P<0.01),IL-4、CD4+CD25+Treg、CD4+CD25+Foxp3+Treg降低(P<0.05);模型组Foxp3、GATA-3mRNA、蛋白表达降低,T-bet mRNA和蛋白升高(P<0.01)。相关性分析显示,T-bet、GATA-3、Foxp3基因和蛋白表达与IL-4、IFN-γ分泌相关(P<0.05)。结论 COPD炎症反应与T-bet、GATA-3、Foxp3表达失衡有一定关系。Objective To observe the change of regulatory T cells（Tregs）, fork head-like transcription factor 3 （ Foxp3）, T box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3） in rat models of chronic obstructive pulmonary disease （COPD）. Methods Thirty rats were randomly divided into control group and model group （n = 15 each）. The rats of model group were developed by lipopolysaccharide （LPS） and smoking. Interleukin-4 （IL-4） and γ-interferon （IFN-y） in serum and bronchoalveolar lavage fluid （BALF） were detected 28 days after modeling by ELISA. Peripheral Tregs were detected by flow cytometry. The expressions of Foxp3, T-bet, GATA gene and protein in lung tissue were observed by reverse transcription PCR and Western blotting, respectively. Results Compared with the control group, the model group had more serious inflammation in lung tissues, expressed the higher levels of IFN-γ in serum and BALF （P 〈0.01 ）, T-bet mRNA and protein in lung tissue, and the lower levels of IL-4, CD4＋ CD25 ＋ Treg, CD4＋ CD25＋ Foxp3- Treg （ P〈0.05）, Foxp3, GATA-3 mRNA and protein （ P 〈 0.01 ）. Correlation analysis showed that there were correlations between T-bet, GATA-3, Foxp3 expressions and IL-4, IFN-γ levels （P 〈 0.05）. Conclusion There is a relationship between inflammation and imbalance of in the expression of T-bet, GATA-3, Foxp3 in COPD.

关 键 词：慢性阻塞性肺疾病 调节性T细胞 叉头状转录因子3 T-BET GATA连接蛋白3 

分 类 号：R563[医药卫生—呼吸系统] R392.11[医药卫生—内科学]