氧化应激对慢性阻塞性肺疾病上皮-间质转化的影响

The Effect of Oxidative Stress on Epithelial-mesenchymal Transition in Chronic Obstructive Pulmonary Disease

目的探究氧化应激与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)上皮-间质转化(epithelial-mesenchymal transition,EMT)的关系。方法收集2015年1月至2017年12月宁夏医科大学总医院心胸外科因肺部肿瘤需行肺叶切除的患者,按2017 GOLD指南分为肺功能正常(对照)组(20例)和COPD组(16例)。通过HE染色观察COPD组及对照组小气道形态学的改变;利用免疫组织化学方法分别检测COPD组及对照组肺组织中EMT标记物E-钙粘连蛋白(E-cadherin,E-Ca)及纤维连接蛋白(fibronectin,FN)的表达情况;采用蛋白免疫印迹法检测COPD组及对照组肺组织中EMT标记物E-Ca和FN的表达情况;采用酶联免疫吸附剂测定法检测COPD组及对照组血清中8-异前列腺素F2α(8-iso-PGF2α)和总抗氧化能力(T-AOC)的浓度。结果免疫组织化学染色结果显示,COPD组气道上皮存在明显的EMT现象,COPD组间质表型标记物FN表达(0.156±0.043)高于对照组(0.072±0.058)(P=0.035),COPD组上皮表型标记物E-Ca表达(0.142±0.068)低于对照组(0.256±0.067)(P=0.016);免疫印迹结果显示,COPD组FN表达(0.60±0.22)高于对照组(0.39±0.22)(P=0.026),COPD组E-Ca表达(0.36±0.20)低于对照组(0.84±0.46)(P=0.003);COPD组血清(8-iso-PGF2α)浓度(45.91±21.17)pg·mL-1高于对照组(29.74±15.88)pg·mL-1(P=0.013),而COPD组血清(T-AOC)浓度(8.49±3.43)IU·mL-1低于对照组(13.35±4.28)IU·mL-1(P=0.001)。结论COPD组织内存在氧化应激及明显的EMT现象,且氧化应激可能通过某种机制参与调控COPD的发生、发展。

Objective To explore the association between oxidative stress and epithelial-mesenchymal transition(EMT)in chronic obstructive pulmonary disease(COPD).Methods Data was gathered from a group of patients undergoing lobectomy for lung tumors admitted to the Department of Cardiothoracic Surgery,General Hospital of Ningxia Medical University from January 2015 to December 2017.According to the GOLD guidelines,patients were divided into normal lung function group(abbreviated as control group,20 cases)and COPD group(abbreviated as COPD group,16 cases).HE staining was used to observe the airway morphology changes in the COPD group and the control group;Immunohistochemical methods were used to detect the expression of EMT markers E-cadherin(E-Ca)and fibronectin(FN)in the lung tissues of the COPD group and the control group,respectively;Western blotting was used to detect The expression of EMT markers E-Ca and FN in the lung tissues of the COPD group and the control group;The enzyme-linked immunosorbent assay was used to detect the expression of 8-isoprostaglandin F2α(8-iso-PGF2α)and total antioxidant capacity(T-AOC)in serum samples of both the COPD group and Control group.Results Immunohistochemical staining showed that the airway epithelium of the COPD group had obvious EMT phenomenon.The expression of mesenchymal phenotype marker FN in the COPD group(0.156±0.043)was higher than that of the control group(0.072±0.058)(P=0.035),and The expression of marker of the epithelial phenotype of the COPD group E-Ca(0.142±0.068)was lower than that of the control group(0.256±0.067)(P=0.016);Western blot also showed that the expression of FN in the COPD group(0.60±0.22)was higher than that of the control group(0.39±0.22)(P=0.026),and the expression of E-Ca in the COPD group(0.36±0.20)was lower than that of the control group(0.84±0.46)(P=0.003).The oxidation product 8-iso-prostaglandin F2α(8-iso-PGF2α)serum concentration of COPD group(45.91±21.17)pg·mL-1 was higher than that of the control group(29.74±15.88)pg·mL-1(P=0.013).The total antioxidant capacity(T-AOC)serum concentration of the COPD group(8.49±3.43)U·mL-1 was lower than the control group(13.35±4.28)U·mL-1(P=0.001).Conclusion There are oxidative stress and obvious EMT phenomena in COPD tissues,and oxidative stress may participate in the occurrence and development of COPD through a certain mechanism.