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IL-33、IL-8和NETs在慢性阻塞性肺疾病患者肺组织中的表达及其意义
张妤,卢献灵
PDF(1295 KB)
PDF(1295 KB)
IL-33、IL-8和NETs在慢性阻塞性肺疾病患者肺组织中的表达及其意义
)Expressions of IL-33, IL-8, and NETs in lung tissue of patients with chronic obstructive pulmonary disease and their significances
)目的 探讨白细胞介素33（IL-33）、白细胞介素8（IL-8）和中性粒细胞胞外诱捕网（NETs）的主要成分髓过氧化物酶（MPO）及瓜氨酸化组蛋白3（CitH3）在慢性阻塞性肺疾病（COPD）患者肺组织中的表达情况，阐明IL-33、IL-8和NETs对COPD发生发展的影响。 方法 选取因肺部结节或肺部肿瘤行肺叶切除术的77例患者作为研究对象，分为不吸烟对照组20例、吸烟对照组18例，不吸烟COPD组19例和吸烟COPD组20例。收集研究对象的肺组织标本，HE染色观察各组患者肺组织病理形态表现，免疫组织化学染色检测各组患者肺组织中IL-33、IL-8、CitH3和MPO蛋白的表达。采用 Spearman 相关分析COPD组患者肺组织中IL-33、IL-8、CitH3和MPO的蛋白表达水平之间及其与肺功能指标、平均内衬间隔（MLI）、平均肺泡数（MAN）和Bosken评分的相关性。 结果 吸烟对照组患者气道Bosken评分明显高于不吸烟对照组（P<0.001）；不吸烟COPD组患者气道Bosken评分和MLI明显高于不吸烟对照组和吸烟对照组（P<0.05），MAN明显低于不吸烟对照组和吸烟对照组（P<0.05）；吸烟COPD组患者气道Bosken评分明显高于不吸烟对照组、吸烟对照组和不吸烟COPD组（P<0.05），MLI明显高于不吸烟对照组和吸烟对照组（P<0.05），MAN明显低于不吸烟对照组和吸烟对照组（P<0.05）。免疫组织化学染色，吸烟COPD组患者肺组织中IL-33蛋白表达水平明显高于不吸烟对照组、吸烟对照组和不吸烟COPD组（P<0.05），IL-8、CitH3和MPO蛋白表达水平明显高于不吸烟对照组和吸烟对照组（P<0.05）；不吸烟COPD组患者肺组织中IL-33、IL-8、CitH3和MPO蛋白表达水平明显高于不吸烟对照组和吸烟对照组（P<0.05）；Spearman相关性分析，COPD组患者肺组织中IL-33蛋白表达水平与第1秒用力呼气容积占用力肺活量的百分比（FEV1/FVC）、第1秒用力呼气容积占预计值百分比（FEV1%pred）和MAN等呈负相关关系（r=－0.406，P<0.05；r=－0.493，P<0.01；r=－0.567，P<0.05），与Bosken评分和MLI等呈正相关关系（r=0.935，P<0.001；r=0.590，P<0.001）；COPD组患者肺组织中IL-8蛋白表达水平与FEV1/FVC、FEV1%pred和MAN等呈负相关关系（r=－0.527，P<0.01；r=－0.497，P<0.01；r=－0.463，P<0.01），与Bosken评分和MLI等呈正相关关系（r=0.557，P<0.001； r=0.486， P<0.01）； COPD组患者肺组织中 CitH3 蛋白表达水平与 FEV1/FVC、FEV1%pred和MAN等呈负相关关系（r=－0.527，P<0.01；r=－0.640，P<0.001；r=－0.531，P<0.01），与Bosken评分和MLI等呈正相关关系（r=0.565，P<0.001；r=0.585，P<0.001）；COPD组患者肺组织中MPO蛋白表达水平与FEV1/FVC呈负相关关系（r=－0.329，P<0.05），与Bosken评分呈正相关关系（r=0.410，P <0.05）；COPD组患者肺组织中IL-8蛋白表达水平与CitH3和MPO蛋白表达水平呈正相关关系（r=0.390，P<0.05；r=0.349，P<0.05）；COPD组患者肺组织中IL-33蛋白表达水平与IL-8、CitH3和MPO蛋白表达水平呈正相关关系（r=0.602，P<0.001；r=0.616，P<0.001；r=0.387，P<0.05）。 结论 IL-33、IL-8 和 NETs在COPD 患者肺组织中的表达水平升高，三者可能参与COPD的慢性炎症，并与疾病严重程度相关。
Objective To discuss the expression levels of interleukin-33 （IL-33）， interleukin-8 （IL-8）， and the major components of neutrophil extracellular traps （NETs）-myeloperoxidase （MPO） and citrullinated histone H3 （CitH3） in lung tissue of the patients with chronic obstructive pulmonary disease （COPD）， and to clarify the effects of IL-33， IL-8， and NETs on the occurrence and development of COPD. Methods Seventy-seven patients underwent lobectomy due to pulmonary nodules or lung tumors were selected as the subjects and divided into non-smoking control group （20 cases）， smoking control group （18 cases）， non-smoking COPD group （19 cases）， and smoking COPD group （20 cases）.The lung tissue samples from the subjects were collected.HE staining was used to observe the pathomorphology of lung tissue of the patients in various groups；immunohistochemisty staining was used to detect the expression levels of IL-33， IL-8， CitH3， and MPO proteins in lung tissue of the patients in various groups； Spearman correlation analysis was used to detect the relationship between expression levels of IL-33， IL-8， CitH3， and MPO proteins in lung tissue of the patients in COPD groups and their correlations with lung function index， mean linear intercept （MLI）， mean alveolar number （MAN）， and Bosken score. Results Compared with non-smoking control group， the airway Bosken score of the patients in smoking control group was significantly increased （P<0.001）； compared with non-smoking control and smoking control groups， the airway Bosken score and MLI of the patients in non-smoking COPD group were significantly increased （P<0.05）， while the MAN was significantly decreased （P<0.05）； compared with non-smoking control group， smoking control group， and non-smoking COPD group， the airway Bosken score of the patients in smoking COPD group was significantly increased （P<0.05）； compared with non-smoking control group and smoking control group， the MLI of the patients in smoking COPD group was significantly increased （P<0.05）， and the MAN was significantly decreased （P<0.05）. The immunohistochemisty staining results showed that compared with non-smoking control group， smoking control group， and non-smoking COPD group，the expression level of IL-33 in lung tissue of the patients in smoking COPD group was significantly increased （P<0.05）； compared with non-smoking control group and smoking control group，the expression levels of IL-8， CitH3， and MPO proteins in lung tissue of the patients in smoking COPD group were significantly increased （P<0.05）. Compared with non-smoking control group and smoking control group， the expression levels of IL-33， IL-8， CitH3， and MPO proteins in lung tissue of the patients in non-smoking COPD group were significantly increased （P<0.05）.The Spearman correlation analysis results showed that there was a negative correlation between the expression level of IL-33 protein and forced expiratory volume in first second/forced vital capacity （FEV1/FVC）， the forced expiratory volume in first second predicted FEV1 （FEV1%pred）， and MAN （r=－0.406， P<0.05； r=－0.493， P<0.01； r=－0.567， P<0.05） in lung tissue of the patients in COPD group， and there was a positive correlation with Bosken score and MLI （r=0.935， P<0.001； r=0.590， P<0.001）；the expression level of IL-8 protein in lung tissue of the patients in COPD group was negatively correlated with the FEV1/FVC， FEV1%pred， and MAN （r=－0.527， P<0.01； r=－0.497， P<0.01； r=－0.463， P<0.01）， and was positively correlated with the Bosken score and MLI （r=0.557， P<0.001； r=0.486， P<0.01）； the expression level of CitH3 protein in lung tissue of the patients in COPD group was negatively correlated with the FEV1/FVC， FEV1%pred， and MAN （r=－0.527， P<0.01； r=－0.640， P<0.001； r=－0.531， P<0.01）， and was positively correlated with the Bosken score and MLI （r=0.565， P<0.001； r=0.585， P<0.001）；the expression level of MPO protein in lung tissue of the patients in COPD group was positively correlated with the FEV1/FVC （r=－0.329， P<0.05）， and was positively correlated with the Bosken score （r=0.410， P<0.05）； the expression level of IL-8 protein was positively correlated with the expression levels of CitH3 and MPO proteins （r=0.390，P<0.05； r=0.349， P<0.05）； the expression level of IL-33 protein was positively correlated with the expression levels of IL-8， CitH3， and MPO proteins （r=0.602，P<0.001； r=0.616，P<0.001； r=0.387， P<0.05）. Conclusion The expression levels of IL-33， IL-8， and NETs in lung tissue of the COPD patients are increased， and they may be involved in the chronic inflammation of COPD and correlated with the severity of the disease.
慢性阻塞性肺疾病 / 白细胞介素33 / 白细胞介素8 / 中性粒细胞胞外诱捕网 / 吸烟
Chronic obstructive pulmonary disease / Interleukin-33 / Interleukin-8 / Neutrophil extracellular traps / Smoking
R563.9
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