FGG与FGA在吸烟所致COPD中的表达及意义  

Expression and significance of FGG and FGA in smoke-induced COPD

作　　者：刘宏军 顾建军 高君吟 王玉秀 闵凌峰 LIU Hong-jun;GU Jian-jun;GAO Jun-yin;WANG Yu-xiu;MIN Ling-feng(Department of Respiratory and Critical Care Medicine,Northern Jiangsu People’s Hospital,Clinical Medical College of Yangzhou University,Yangzhou 225001,China)

机构地区：[1]扬州大学临床医学院,苏北人民医院呼吸与危重症科,江苏扬州225001

出　　处：《中国病理生理杂志》2021年第10期1868-1875,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81870033,No.81302016);江苏省自然科学基金资助项目(No.BK20130455);江苏省“六大人才高峰”计划(No.WSN-106)。

摘　　要：目的:筛选慢性阻塞性肺疾病(COPD)的关键基因,寻找潜在生物标志物和新的治疗靶点。方法:从GEO数据库选择3个人肺组织来源的mRNA表达数据集,应用R语言和GEO2R筛选COPD患者肺组织与表型正常肺组织的差异表达基因。对DAVID6.8数据库行GO分析,选择关键基因。在来自GEO数据库的人肺组织、小气道上皮、小鼠肺组织及TCGA数据库的病理正常的癌旁肺组织这4组数据中,分析关键基因的mRNA表达与吸烟及COPD的关系。将16只C57BL/6J雄性小鼠随机均分为对照组和吸烟组,对照组小鼠予新鲜空气,吸烟组小鼠于自制染毒箱中予以香烟烟雾暴露1 h/d,每周5 d,连续处理24周。收集样本,采用ELISA法检测小鼠支气管肺泡灌洗液及肺组织中白细胞介素6(IL-6)水平,免疫组化方法分析肺组织中纤维蛋白原γ链(FGG)、纤维蛋白原α链(FGA)、α-平滑肌肌动蛋白(α-SMA)和E-钙黏蛋白(E-cadherin)的表达。结果:人肺组织FGG与FGA的mRNA表达水平在吸烟者中均高于非吸烟者,在COPD患者中均高于表型正常吸烟者,其中FGG表达水平随吸烟剂量增加而升高,在小鼠肺组织,前述结果仍成立,TCGA数据与小鼠肺组织数据都显示戒烟可以缓解这个趋势,但需要较长时间。仅在人肺组织中,FGG与FGA的mRNA表达量比值有助于识别COPD患者,而在人小气道上皮样本中,FGA表达水平有助于识别早期COPD。动物实验显示,香烟烟雾暴露可致小鼠支气管肺泡灌洗液中IL-6水平及肺组织中IL-6、FGG、FGA和α-SMA的水平升高,E-cadherin的水平下降。结论:FGG与FGA在肺组织中的表达与吸烟及COPD显著相关,FGG/FGA有助于早期识别COPD,香烟烟雾可能通过上调IL-6刺激小鼠肺组织FGG与FGA的合成进而影响上皮-间充质转化水平参与COPD的发生。戒烟有助缓解吸烟引起的基因表达异常。AIM:To screen the key genes of chronic obstructive pulmonary disease(COPD)and to look for potential biomarkers and new therapeutic targets.METHODS:Three human lung tissue-derived transcriptome data sets were selected from the GEO database,and R language and GEO2 R were used to screen the differential expression genes between COPD patients and normal human lung tissues. GO analysis was performed on the DAVID6. 8 database to select key genes. In 4 data sets of human lung tissue,small airway epithelium,mice lung tissue from GEO database,and pathologically paracancerous normal lung tissue from TCGA database,the relationship between key genes and smoking and COPD were analyzed. C57 BL/6 J male mice(n=16)were randomly divided into control group and cigarette smoke group,8 in each group. The mice in control group were given fresh air,and the mice in cigarette smoke group were exposed to cigarette smoke for 1 h/d,5 d/week in a self-made poisoning box. After treatment for 24 weeks,interleukin-6(IL-6)levels in bronchoalveolar lavage fluid(BALF)and lung tissue were detected by ELISA. fibrinogen gamma chain(FGG),fibrinogen alpha chain(FGA),α-smooth muscle actin(α-SMA)and E-cadherin expression was analyzed by immunohistochemistry.RESULTS:The mRNA expression of FGG and FGA in human lung tissue were higher in smokers than that in nonsmokers,and higher in the lung tissues of COPD patients than that in normal phenotypic smokers. The FGG expression level was increased with the increase in smoking dose. In mouse lung tissue,the above results were still valid. Both TCGA and mouse lung tissue data showed that smoking cessation alleviated this trend,but it took time. Only in human lung tissue,the ratio of FGG to FGA expression was helpful to identify COPD patients,while in human small airway epithelial samples,FGA expression level helps to identify early COPD. The results of animal experiment showed that smoking increased the levels of IL-6 in BALF and lung tissue,and increased the levels of FGG,FGA and α-SMA and reduced the Ecadhe

关 键 词：吸烟 慢性阻塞性肺疾病 FGG FGA 上皮-间充质转化 白细胞介素6 

分 类 号：R563[医药卫生—呼吸系统] R363.2[医药卫生—内科学]