转化生长因子-β亚型在慢性阻塞性肺疾病急性加重期患者中的表达研究  

Expression of Transforming Growth Factor-βIsoforms in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

作　　者：江山 袁竞 秦超 戴曦 JIANG Shan;YUAN Jing;QIN Chao(Department of Respiratory and Critical Care Medicine,The People’s Hospital of Dujiangyan,Chengdu,Sichuan,611830,China)

机构地区：[1]都江堰市人民医院呼吸与危重医学科,四川成都611830 [2]泸州市人民医院检验科,四川泸州646000 [3]西南医科大学附属医院呼吸与危重症医学科,四川泸州646000

出　　处：《黑龙江医学》2022年第24期2949-2953,共5页Heilongjiang Medical Journal

基　　金：西南医科大学校级重点科研基金资助项目(0903-00031247)。

摘　　要：目的:研究转化生长因子β亚型1/β亚型2/β亚型3(TGF-β1/β2/β3)在慢性阻塞性肺疾病(COPD)患者诱导痰中的表达与作用。方法:选取2019年1月—2021年12月都江堰市人民医院就诊的14例慢阻肺急性加重期患者、15例慢阻肺稳定期患者以及8例正常志愿者作为实验对象,采集实验对象的诱导痰行炎细胞分类计数,分离提取诱导痰中巨噬细胞并免疫荧光标记Smad2/3,酶连免疫吸附(ELISA)检测痰液中TGF-β1/β2/β3水平,纤维支气管镜下行气道黏膜上皮活检,马松(MASSON)染色以及蛋白印迹法(Western blot)检测黏膜上皮中TGF-β、Smad2/3蛋白表达水平。结果:(1)慢阻肺急性加重期组巨噬细胞计数、Smad2/3的表达强度、诱导痰中TGF-β1/β2/β3的表达水平,以及气道上皮胶原纤维增生程度均高于COPD稳定期组和正常对照组。(2)COPD患者的诱导痰中TGF-β1/β2的表达水平与巨噬细胞数量、Smad2/3的平均荧光强度值呈正相关,差异有统计学意义(r=0.8888、0.8938、0.6199、0.616、P<0.01),而与患者肺功能呈负相关,差异有统计学意义(r=-0.810、-0.7397,P<0.01)。(3)TGF-β3的表达水平与巨噬细胞数量和患者肺功能没有显著相关性。(4)Western blot结果显示,与COPD组比较,慢阻肺急性加重期(AECOPD)组气管黏膜TGF-β及其下游信号通路相关蛋白Smad2/3的表达均明显升高。结论:TGF-β1/β2可作为监测病情的指标,其方式可能是通过Smad2/3蛋白信号通路的转导参与COPD患者的气道重塑,而TGF-β3在慢阻肺急性加重期患者诱导痰中亦有升高,但临床价值不大,其具体作用方式的机制仍需要进一步的研究。Objective:To study the expression and effect of transforming growth factor beta isoform 1/beta isoform 2/beta isoform 3(TGF-beta1/beta2/beta3)in induced sputum of patients with chronic obstructive pulmonary disease(COPD).Methods:A total of 14 patients with acute exacerbation of COPD,15 patients with stable COPD and 8 normal volunteers were randomly selected.The induced sputum of the experimental subjects was collected for classification and counting of inflammatory cells,and the macrophages in the induced sputum were isolated and extracted and labeled with Smad2/3 by immunofluorescence.The levels of TGF-β1/β2/β3 in sputum were detected by enzyme-linked immunosorbent assay(ELISA).Under fiberoptic bronchoscopy,the airway mucosal epithelium was biopsied.The expression levels of TGF-βand Smad2/3 in mucosal epithelium were detected by Masson staining and Western blot.Results:(1)The macrophage count,the expression intensity of Smad2/3,the expression level of TGF-β1/β2/β3in induced sputum,and the degree of airway epithelial collagen fiber hyperplasia in the acute exacerbation group of COPD were higher than those in the stable COPD group and the normal control group.(2)The expression level of TGF-β1/β2 in the induced sputum of patients with COPD was positively correlated with the number of macrophages and the mean fluorescence intensity of Smad2/3,and the difference was statistically significant(r=0.8888,0.8938,0.6199,0.616,P<0.01),and was negatively correlated with the lung function of patients,the difference was statistically significant(r=-0.810,-0.7397,P<0.01).(3)The expression level of TGF-β3 was not significantly correlated with the number of macrophages and the lung function of patients.(4)Western blot results showed that compared with the COPD group,the expressions of TGF-βand its downstream signaling pathway-related proteins Smad2/3 in the tracheal mucosa of the acute exacerbation of COPD(AECOPD)group were significantly increased.Conclusion:TGF-β1/β2 can be used as an indicator to monitor the diseas

关 键 词：慢阻肺急性加重期 COPD 肺泡巨噬细胞 

分 类 号：R723.11[医药卫生—儿科]