慢性阻塞性肺疾病患者肺组织中ATF3与ATF4对γ-GCS表达的影响

Study on the influence on expression of γ-GCS in ATF3 and ATF4 in lung tissue of patients with chronic obstructive pulmonary disease

目的探究慢性阻塞性肺疾病(COPD)患者肺组织中转录活化因子3(ATF3)与转录活化因子4(ATF4)对γ-谷氨酰半胱氨酸合成酶(γ-GCS)表达的影响。方法本研究采用回顾性分析方法,选择2014~2016年收治的160例肺部疾病患者作为研究对象,将经胸部X线或CT检查确诊为COPD者列为观察组(80例),将非COPD者列为对照组(80例)。观察两组光镜下肺病理形态学改变、肺功能指标和吸烟史。经原位杂交分析两组肺组织中的ATF3、ATF4、γ-GCS-HS水平,采用免疫组化法检测肺组织中的ATF3、ATF4、γ-GCS-HS蛋白表达,并采用直线相关法,分析肺组织ATF3、ATF4蛋白与γ-GCS-HS表达的相关性及肺组织ATF3、ATF4、γ-GCS-HS蛋白与肺功能之间的关系。结果经HE法,光镜下可见观察组肺组织标本有病理形态学改变,而对照组无形态学变化;观察组肺功能指标低于对照组(P<0.05),观察组吸烟史多于对照组(P<0.05)。经原位杂交法检验,观察组中的ATF3、ATF4、γ-GCSHS的mRNA表达水平高于对照组,差异有统计学意义(P<0.05)。经免疫组化检测,观察组中的ATF3、ATF4、γ-GCS-HS蛋白的表达水平高于对照组,差异有统计学意义(P<0.05)。经直线相关法分析,ATF3、ATF4蛋白表达与γ-GCS-HSmRNA及其蛋白呈正相关关系(P<0.01);ATF3、ATF4、γ-GCS-HS蛋白与肺功能各指标呈正相关关系(P<0.01)。结论 COPD患者的ATF3、ATF4表达明显上调可影响调控γ-GCS表达,从而使γ-GCS表达上调,以发挥抗氧化作用。

Objective To explore the activation of transcription factor 3(ATF3)and transcription factor 4(ATF4)in lung tissue on the expression of gamma-glutamine cysteine synthase(γ-GCS)in patients with chronic obstructive pulmonary disease.Methods The clinical data of 160 patients with pulmonary diseases treated in 2014 to 2016 were retrospectively reviewed and studied,80 cases were confirmed by chest X-ray examination or CT scanning for COPD as observation group(80 cases),and other 80 cases without COPD were listed in control group.The changes in morphological features under microscopy,pulmonary function indexes and smoking history were observed and recorded.Levels of ATF3,ATF4 andγ-GCS-HS in pulmonary tissues were examined by in situ hybridization.Immunohistochemical analysis was performed to detect the expression of ATF3,ATF4 andγ-GCS-HS protein,then they were analyzed by linear correlation method,and lung tissue ATF3,ATF4 transcription and the relationship between expression ofγ-GCS-HS activation factor,γ-GCS-HS protein and lung function were analyzed.Results After HE staining,the changes in pathomorphism in visible lung tissue samples in observation group had been observed,while no morphological change had been seen in control group.Lung function in observation group was lower than that of control group(P<0.05),patients with smoking history in observation group were more than those of control group(P<0.05).When check by in situ hybridization,the expression levels of ATF3,ATF4 andγ-GCS-HS and mRNA in observation group were higher than those of control group,and the difference was statistically significant(P<0.05).By immunohistochemical detection,ATF3,ATF4,gamma GCS-and HS protein expression level in observation group were higher than those of control group,and the difference between these 2 groups was statistically significant(P<0.05).Analysis with the linear correlation method,the expression levels of ATF3 and ATF4 protein were positively correlated with gamma GCS-HSmRNA and its protein(P<0.01).The levels of ATF3,ATF4 and gamma-GCS-HS protein were positively correlated with lung function index(P<0.01).Conclusion The expresson levels of ATF3 and ATF4 in COPD patients are significantly raised,thus they can affect the regulation of expressiion ofγ-GCS,so that it can influence the expression ofγ-GCS,in order to play the role of antioxidant.