慢性阻塞性肺疾病患者诱导痰中白介素8、白三烯B4、髓过氧化物酶的变化以及噻托溴铵对其的影响

Changes of interleukin-8, leukotriene B4 and myeloperoxidase in induced sputum of patients with chronic obstructive pulmonary disease and the effects of tiotropium

目的探讨慢性阻塞性肺疾病（COPD）患者中白三烯B4（LTB4）、白介素8（IL-8）、髓过氧化物酶（MPO）的变化及噻托溴铵对其的影响，进一步验证噻托溴铵是否有抗炎作用。方法选中度至极重度COPD稳定期患者30例为噻托溴铵治疗前组，予吸入噻托溴铵30d，剂量18μg·d^-1，为噻托溴铵治疗后组。并选10例健康查体者为对照组，本组无任何干预措施。三组均进行血气分析、肺功能检查和诱导痰沉渣细胞计数和痰上清液ELISA法测定IL-8、LTB4、MPO。采用独立样本t检验及配对t检验，Pearson及Spearman相关等分析。结果噻托溴铵组与健康对照组痰细胞分类、IL-8[（777．05±392．43）pg·ml^-1 vs（311．27±135．93）pg·ml^-1]、LTB4[（96．70±29．13）Pg·ml^-1 vs（20．60±9．89）pg·ml^-1]、MPO[（23．50±16．77）U·ml^-1 vs（10．52±3．55）U·ml^-1]指标比较，差异均具有统计学意义。噻托溴铵治疗前后痰细胞分类比较，差异无统计学意义，IL-8[（777．05±392．43）pg·ml^-1 vs（408．93±339．14）pg·ml^-1]、LTB4[（96．70±29．13）pg·ml^-1 vs（43．69±16．49）pg·ml^-1]差异有统计学意义。相关分析示IL-8与PaO2（r=-0．411）、肺功能指标FEV1 ％pred（r=-0．440）、FVC％pred（r=-0．440）、FEV1／FVC％（r=-0．417）有相关性。结论COPD患者诱导痰中炎性细胞及炎性因子与健康对照组比较，差异有统计学意义。噻托溴铵对COPD患者诱导痰中IL-8、LTB4有降低作用。

Objective To investigate the changes of interleukin-8（IL-8） ,leukotriene B4（LTB4） and myeloperoxidase（MPO） in induced sputum of patients with chronic obstructive pulmonary disease（COPD） and the effects of tiotropium. To identify the anti-inflammatory function of tiotropium. Methods We admitted 30 moderate to very severe stable COPD patients as tiotropium pre-therapy. At the same time, the same patients as tiotropium post-therapy when they were received inhaled tiotropium 18μg·d^-1 for one month. Ten age-matched healthy objects were included as controls. The following measurements were performed for each group ： arterial blood gases, pulmonary function, cell diferentials in induced sputum, and concentrations of IL-8,LTB4 and MPO in induced sputum by using enzyme linked immunosorbent assay （ELISA）. Analysis with Independent-Samples T Test, Paired-Samples T Test and Pearson correlate coefficients and so on. Results The concentrations of IL-8,LTB4, MPO in induced sputum in tiotropium pre-therapy group were significantly higher than those in group controls IL-8 [（777.05±392.43） pg · ml^-1 VS （311. 27±135. 93） pg · ml^-1],LTB4 [（96.70±29. 13） pg · ml^-1 vs （20.60±9.89） pg · ml^-1,MPO [（23.50±16.77） U· ml^-1 vs （10.52±3.55） U· ml^-1],respectively. And the concentrations of IL-8, LTB4 in tiotropium pre-therapy group were also significantly higher than those in tiotropium post-therapy group IL-8E（777. 05± 392. 43） pg· ml^-1 vs （408.93±339.14） pg · ml^-1],LTB4 E （96.70±29.13） pg· ml^-1 vs （43.69±16.49） pg· ml^-1]. There were no significant changes either in cell counts or in the level of MPO in induced sputum. IL-8 was correlated with PaO2 （ r = -0. 411） ,FEV1（ r = -0. 440）, FVC% （ r = - 0. 440）, FEV1/FVC% （ r = - 0. 417 ）, respectively. Conclusions Cell diferentials, IL-8, LTB4 and MPO in induced sputum are different between COPD patients and healthy controls. Inhaled tiotropium therapy reduces the levels of IL-8,LTB4 in induced sputum in COPD patients.