摘要
目的研究慢性阻塞性肺疾病(COPD)患者气道局部尿激酶型纤溶酶原激活物(u-PA)系统状态及其病理生理意义。方法(1)诱导痰检测临床稳定期COPD患者(诱导痰COPD组)56例,平均年龄(51±11)岁,第一秒用力呼气容积占预计值百分比(FEV1占预计值%)为(53.5%±14.4)%,诱导痰健康对照组26名,平均年龄(46±9)岁,FEV1占预计值%为(85.1±1.0)%;采用酶联免疫吸附法测定诱导痰中u-PA、尿激酶型纤溶酶原激活物受体(u-PAR)、纤溶酶原激活物抑制剂1(PAI-1)和白细胞介素8(IL-8)、γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)水平;(2)肺组织病理COPD并肺大疱接受手术治疗患者(免疫组化COPD组)11例,平均年龄(53±7)岁,FEV1占预计值%为(58.3±6.6)%;非COPD因肺部局灶病变接受手术治疗患者(非免疫组化COPD对照组)10例(其中炎性假瘤3例、错构瘤5例、结核球2例),平均年龄(47±12)岁,FEV1占预计值%为(84.3±1.6)%。采用免疫组化检测u-PA、u-PAR、PAI-1在肺组织中的细胞表达。结果(1)诱导痰COPD组诱导痰中可溶性u-PAR、PAI-1和IL-8水平分别为(570±614)ng/L、(6162±9247)ng/L、(12370±17292)ng/L,与健康对照组[(97±74)ng/L、(574±731)ng/L、(1868±1905)ng/L]比较差异有统计学意义(t值分别为5.629、4.346、4.486,P均<0.01);(2)相关分析诱导痰COPD组诱导痰中可溶性u-PAR和PAI-1水平分别与IL-8呈正相关(r值分别为0.483、0.770,P均<0.01),可溶性PAI-1水平与患者FEV1占预计值%呈负相关(r=-0.272,P<0.05);(3)免疫组化免疫组化COPD组u-PAR表达[(49±16)%]见于肺泡上皮细胞、巨噬细胞、中性粒细胞以及淋巴细胞,而免疫组化非COPD对照组[(33±18)%]表达着色浅淡,主要见于肺泡上皮细胞,两组阳性表达率比较差异有统计学意义(t=2.213,P<0.05);免疫组化COPD组PAI-1表达[(61±16)%]见于成纤维细胞、巨噬细胞和中性粒细胞,而免疫组化非COPD组[(37±16)%]表达着色浅淡,主要见于成纤维细胞,两组阳性表达率比较差异有统计学意义(t=3.419P<0.05)。结论u-PA系统成分是COPD气道局部重要的炎性介质,其中PAI-1在COPD的组织重塑中可能具有重要作用。
Objective To investigate the state and the pathophysiologic significances of urinary plasminogen activator system components in airways of patients with chronic obstructive pulmonary disease （COPD）. Methods （1） Assay of induced sputum： 56 patients with COPD in stable clinical conditions （ COPD group） , aged （ 51 ± 11 ） years with forced expiratory volume in one second of predicted % （ FEV1 % predicted） （53.5 ± 14. 4 ）% predicted, and 26 healthy control subjects （control group ）, aged （46 ± 9 ） years; FEV1% predicted （85. 1 ± 1.0）% were studied. Levels of urokinase plasminogen activator system components in induced sputum, urokinase plasminogen activator （u-PA）, urokinase plasminogen activator receptor （ u-PAR ） , plasminogen activator inhibitor-1 （ PAI-1 ） and interleukin-8 （ IL-8 ）, interferon-γ （IFN-γ） , tumor necrosis factor （TNF-α） , and intefleukin-10 （IL-10） were determined by enzyme linked immunosorbent assay. （2） Pathological section of resected lung tissue： The study subjects included 11 patients receiving lung lobectomy for COPD with emphysematous bullae, aged （53 ± 7 ）yeas, FEV1 % predicted （58. 3 ±6.6）% ; as well as 10 non-COPD patients receiving lung lobectomy for local lesions withnormal lung function, aged （ 47 ± 12 ） years, FEV1% predicted （ 84. 3± 1.6 ） % , of which 3 were inflammatory pseudotumor, 5 were hamartoma, and 2 tuberculoma as the control. Cell expression of u-PA, u-PAR , PAI-1 in the pulmonary pathologic sections was investigated by immunohistochemistry. Results Induced sputum of COPD patients showed significant increase in u-PAR, PAI-1, and IL-8 compared to the control subjects, （ 570 ± 614 ） ng/L vs （ 97 ± 74） ng/L （ t = 5. 629, P 〈 0. 01 ）, （ 6 162 ± 9 247） ng/L vs （574±731） ng/L （t=4.346, P〈0.01） and （12370±17292） ng/Lvs （1 868± 1905） ng/L （t= 4. 486, all P 〈 0. 01 ）; and there were no differences in u-PA, IFN-γ, TNF-α, and IL-10. Correlation analysis showed that u-PAR and PAI were positively correlated with IL-8 in COPD patients （ r = 0. 483, 0. 770, all P 〈 0. 01 ）, while PAI negatively correlated with FEV1% （ r = - 0. 272, P 〈 0. 05 ） . No correlation was found in healthy control subjects, u-PAR was localized in alveolar epithelial cells, macrophages, neutrophils and lymphocytes in COPD subjects ,while u-PAR was mainly localized in alveolar epithelial cells in the control subjects. The ratio of positive expression in alveolar epithelial cells of control subjects was significantly lower than in that of COPD subjects （33 ± 18 ）% vs （49 ± 16 ）% （t = 2. 213, P 〈 0. 05 ） , while the detectable intensity of expression in these cells of control subjects was also weaker than that of COPD subjects. PAI-1 was localized in fibroblasts, macrophages and neutrophils in COPD subjects, while mainly localized in fibroblasts in control subjects; the ratio of positive expression in fibroblasts in control subjects was also significantly lower than that in COPD subjects （37 ± 16）% vs （61 ± 16）% （t = 3. 419, P 〈0. 05 ）, meanwhile the detectable intensity of expression in these cells of control subjects was weaker than that of COPD one. Conclusion u-PA system components are important inflammatory mediators in airways of COPD. PAI-1 is most likely to play a significant role in airway remodelling of COPD.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2006年第11期723-726,共4页
Chinese Journal of Tuberculosis and Respiratory Diseases
