肺功能正常吸烟者和慢性阻塞性肺疾病患者肺动脉炎症和小气道炎症的相关性研究

The relationship between pulmonary arterial and small airway inflammation in smokers with and without chronic obstructive pulmonary disease

目的 研究肺功能正常吸烟者和慢性阻塞性肺疾病（慢阻肺）患者肺腺泡动脉炎症与小气道炎症的相关性.方法 选取广西医科大学第一附属医院心胸外科因周围型肺癌行肺叶切除术的33例患者,其中男30例,女3例,年龄（61±9）岁,分为A组（肺功能正常不吸烟组,10例）、B组（肺功能正常吸烟组,13例）、C组（吸烟慢阻肺稳定期组,10例）,取手术切除的远离肺癌病灶的正常肺组织,HE和维多利亚蓝＋范吉逊染色检测各组肺腺泡肌型动脉（MA）及小气道病理形态改变,测量MA管壁厚度并计算小气道病理积分,使用免疫组织化学方法检测淋巴细胞在MA和小气道的浸润水平,并分析MA炎症和小气道炎症的相关性.结果 3组患者MA管壁厚度分别为（119±11）、（139±25）和（172 ±28）μm,小气道病理积分分别为（49±10）、（101±34）和（163 ±36）分,B组和C组均明显高于A组,且C组明显高于B组（均P ＜0.05）.B组和C组CD3＋总T细胞、CD8＋ T细胞在MA内膜、中膜、外膜及小气道上皮层、固有层、外膜层浸润较A组均增加,以MA外膜及小气道外膜层CD8＋T细胞浸润为明显（均P＜0.05）;C组较A组CD4T细胞在小气道上皮层、固有层、外膜层表达也增高（均P＜0.05）,气道壁全层CD4/CD8＋降低（P＜0.01）,而CD4＋T细胞在3组MA各层比较差异均无统计学意义（均P ＞0.05）;B淋巴细胞在3组MA及小气道各层比较差异均无统计学意义（均P ＞0.05）.MA管壁CD3＋总T细胞、CD8＋T细胞浸润程度与小气道病理总积分呈正相关（r值分别为0.431、0.633,均P＜0.05）;CD3＋总T细胞、CD8＋T细胞在MA管壁浸润程度与其在小气道壁的浸润程度呈正相关（r值分别为0.655、0.725,均P＜0.01）;MA管壁及小气道壁CD8＋T细胞浸润程度与MA管壁厚度呈正相关（r值分别为0.589、0.556,均P＜0.01）.结论 肺功能正常吸烟者和慢阻肺患者肺动脉炎症和小气道炎症均是以管壁全层尤其是外膜为主,主要以CD8＋T细胞浸润为特征的同一性质的炎症,且两者密切相关,是慢阻肺全肺炎症的一部分,共同促进慢阻肺的发展.

Objective To investigate the relationship between pulmonary arterial and small airway inflammation in smokers with normal lung function and smokers with chronic obstructive pulmonary disease （COPD）.Methods Patients requiring lung resection for peripheral lung cancer were divided into group A （nonsmokers with normal lung function,n =10）,group B （smokers with normal lung function,n =13） and group C （smokers with stable COPD,n =10）.Normal pulmonary tissue was obtained more than 5 cm away from cancer lesion.The pathomorphological changes of the pulmonary muscularized arteries（MA） and small airways were observed by HE and Victoria blue-Van Gieson＇ s stains.Lymphocytes infiltrated in the MA and small airways were observed by immunohistochemical methods.The characteristics and the correlations between pulmonary arterial inflammation and small airway inflammation were analyzed.Results The thickness of MA wall in the three groups was （119 ± 11）,（139 ± 25） and （172 ± 28）μm respectively.The total small airway pathology score was （49 ± 10）,（101 ± 34） and （163 ± 36） respectively.The score in group B and C was significantly higher than that in group A （P 〈 0.05）,and the thickness of MA wall and total small airway pathology score in group C was significantly higher than that in group B （P 〈 0.05）.The degree of CD3＋ T-lymphocytes and CD8＋ T-lymphocytes infiltration in the intima,media and adventitia of MA and epithelial layer,lamina propria and adventitia of small airway in group B and C was more significant than that in group A,especially CDs8＋ T-lymphocytes infiltration in adventitia of MA and small airway （P 〈 0.05）.Expression of CD4＋ T-lymphocytes on epithelial layer,lamina propria and adventitia of small airway in group C was higher than that in group A （P 〈 0.05）,but the CD4＋/CDs＋ ratio in the whole layer of airway wall declined （P 〈 0.01）.Among three groups,the infiltration of B-lymphocytes in three layers compared each other had no statistical differences （P 〉 0.05）.The infiltration of CD3＋ Tlymphocytes and CD8＋ T-lymphocytes in the whole layer of MA was positively correlated with the total small airway pathology score respectively （r =0.431,0.633,P 〈 0.05）,and the degree of CD3＋ T-lymphocytes and CD8＋ T-lymphocytes infiltration in MA showed positive correlation with that in small airway （r =0.655,0.725,P 〈 0.01）.The degree of CD8＋ T-lymphocytes infiltration in MA and small airway was positively correlated with thickness of MA （r =0.589,0.556,P 〈 0.01）.Conclusions Both in smokers with normal lung function and smokers with stable COPD,CDs＋ T-lymphocytes infiltration in the whole layer of pulmonary arteries and small airways is the same kind of inflammation,mainly in the adventitia of pulmonary arteries and small airways.They are a part of pulmonary inflammation in COPD and promote the development of COPD.