吸烟慢性阻塞性肺疾病患者肺动脉白细胞介素-16和CXC趋化因子受体3表达的意义

目的 探讨IL-16、CXC趋化因子受体3(CXCR3)在正常吸烟者和吸烟慢性阻塞性肺疾病(COPD)患者肺动脉表达的意义.方法 将周围型肺癌Ⅰ期～Ⅲa期需要手术治疗的患者分为不吸烟肺功能正常组(10例)、吸烟肺功能正常组(13例)、吸烟COPD稳定期组(10例),取3组患者的肺组织,观察肺腺泡肌型动脉(MA)的病理改变,ELISA检测肺组织匀浆IL-16水平;免疫组化法检测IL-16和CD_3~+T细胞、CD_4~+T细胞、CD_8~+T细胞以及CXCR3在MA表达水平;相关分析MA IL-16、CXCR3表达水平与临床和肺功能主要指标的相关性.结果 (1)吸烟COPD稳定期组肺组织匀浆IL-16水平较不吸烟肺功能正常组、吸烟肺功能正常组显著升高,吸烟肺功能正常组较不吸烟肺功能正常组升高;(2)吸烟肺功能正常组、吸烟COPD稳定期组较不吸烟肺功能正常组IL-16、CXCR3在MA表达范围和程度均增高,且吸烟COPD稳定期组与吸烟肺功能正常组比较,差异有统计学意义(P<0.01);(3)相关分析:吸烟COPD稳定期组MA IL-16表达水平与CD_3~+T细胞计数、CD_8~+T细胞计数、CXCR3表达水平呈正相关(r分别为0.639、0.803、0.696,P<0.05或P<0.01),与吸烟指数、BODE指数呈正相关(r分别为0.737、0.704,P值均小于0.05),与第1秒钟用力呼气容积(FEV_1)占预计值的百分比、6 min步行距离(6MWD)呈负相关(r分别为-0.803、-0.787,P值均小于0.01);吸烟COPD稳定期组MA CXCR3表达水平与吸烟指数、BODE指数呈正相关(r分别为0.650、0.767;P值均小于0.05),与FEV_1、6MWD呈负相关(r分别为-0.778、-0.774;P值均小于0.01).结论 (1)吸烟肺功能正常组和吸烟COPD稳定期组MA IL-16、CXCR3主要在淋巴细胞内表达,其表达水平与CD_+~8T细胞密切相关.提示IL-16通过CXCR3趋化CD_+~8T细胞,参与对COPD肺动脉炎症的调节;(2)肺动脉IL-16、CXCR3的表达与临床及肺功能的主要指标密切相关,提示肺动脉炎症是影响COPD进程的一个重要因素,抑制肺动脉炎症应成为COPD综合防治的一个重要方面.

The changes and significance of interleukin-16 and CXC chemokine receptor 3 expression in pulmonary artery of smokers with chronic obstructive pulmonary disease

Objective To study the pathological characteristics of interleukin-16 (IL-16) and CXC chemokine receptor 3 (CXCR3) in pulmonary artery of smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). Methods We examined surgical specimens from three groups of subjects undergoing lung resection for localized pulmonary lesions: group NS(nonsmokers with normal lung function, n=10); group S (smokers with normal lung function, n=13); group COPD (smokers with stable COPD, n=10). The clinical datas including blood gas analysis, pulmonary function,BMI, smoking index, BODE index, six-minute-walk distance (6MWD), Medical Research Council dyspened scale (MRC), St. George Respiratory Questionnaire (SGRQ) were recorded in all subjects before the operation. We applied technique of hematoxylin-eosin staining to observe pathomorphological changes of the pulmonary arteries. The concentration of IL-16 in lung tissues were measured by ELISA. Muscularized arteries were examined with immunohistochemical methods to identify T-lymphocytes (CD_3), CD_4 T-lymphocytes, CD_8 T-lymphocytes, IL-16, CXCR3. The correlation of IL-16 and CXCR3 in muscnlarized arteries in smokers with stable COPD were analysed. Results (1) The group COPD showed the highest concentration of IL-16 in lung tissue (P <0. 01) . The concentration of IL-16 in group S was higher than group NS (P<0.05). (2) Both in group S and group COPD, the percentage of the muscularized arteries that contained CXCR3 and IL-16 were increased as compared with group NS (P < 0. 01). Moreover there were statistical significance have been observed between group COPD and group S(P < 0.01). (3) The intensity of IL-16 infiltrating the muscularized arteries in group COPD showed a positive correlation with CD_3~+ T-lymphocytes, CD_8~+ T-lymphocytes, CXCR3 (r=0.639,0. 803,0. 696; P < 0. 05 or P < 0. 01), smoking index, BODE index (r= 0.737,0. 704; P < 0. 05). There was inverse relationship between the content of IL-16 in the muscularized arteries in group COPD and forced expiratory volume in one second% predicted (FEV_1 % Pred) and 6MWD (r=-0.803,-0.787; P<0.01). We also found the intensity of CXCR3 infiltrating the muscularized arteries in group COPD showed a positive correlation with CD_3~+ T-lymphocytes,CD_8~+ T-lymphocytes(r=0.650,0.767; P<0.05), smoking index, BODE index (r=0.650,0.767; P< 0.05). There was inverse relationship between the content of CXCR3 in the muscularized arteries in group COPD and FEV_1 % Pred and 6MWD (r=-0.778,-0.774;P<0.01). Conclusions (1) Both in group S and group COPD, IL-16 and CXCR3 were mainly expressed in lymphocytes which were correlated with CD_8~+ T-lymphocytes infiltrating the muscularized arteries. There were some suggestion that IL-16 prohaly recruited CD_8~+ T-lymphocytes into muscularized arteries by enhancing the expression of CXCR3. (2) The intensity of IL-16 and CXCR3 were correlated with the index of clinical and pulmonary function that suggested pulmonary arterial inflammation might be one of the key factors associated with the progression of COPD, and inhibiting the pulmonary artery inflammation played an important role in prevention and cure of COPD.