白三烯B4在慢性阻塞性肺疾病中的变化与氨茶碱对其的影响  

Changes of leukotriene B4 in chronic obstructive pulmonary disease and effects of theophylline on leukotriene B4

作　　者：丁艳苓[1] 姚婉贞[1] 郑杰[2] 朱元莉[3] 刘政[4] 

机构地区：[1]北京大学第三医院呼吸科,北京100083 [2]北京大学基础医学院病理学系 [3]北京大学第三医院病理科 [4]中国石油天然气集团公司中心医院呼吸科

出　　处：《北京大学学报（医学版）》2005年第4期393-397,共5页Journal of Peking University:Health Sciences

摘　　要：目的:探讨白三烯B4(leukotrieneB4,LTB4)在慢性阻塞性肺疾病(chronicobstructivepulmonarydisease,COPD)气道局部与血循环中的变化与氨茶碱对其影响。方法:32只雄性Wistar大鼠按随机数字表法分成A组(正常对照组)、B组(COPD组)、C组(氨茶碱低剂量组)、D组(氨茶碱高剂量组),每组8只。测定各组大鼠肺功能,观察肺组织病理改变,对支气管肺泡灌洗液(bronchoalveolarlavagefluid,BALF)行细胞计数与分类,并检测BALF、血浆及肺组织匀浆液中白细胞介素-8(IL-8)、LTB4的水平。结果:COPD大鼠BALF中LTB4水平较正常对照组明显增高,并与中性粒细胞百分比(r=0.794,P=0.007)、IL-8水平呈显著正相关(r=0.863;P=0.012),与呼气峰流速(peakexpiratoryflow,PEF)呈显著负相关(r=-0.718,P=0.028),并与小气道病变中的炎症细胞浸润评分显著正相关(r=0.836,P=0.036)。氨茶碱的干预可降低COPD大鼠BALF中LTB4水平及中性粒细胞%,改善小气道黏液细胞渗出,杯状细胞化生,炎症细胞浸润,纤维结缔组织增生,平滑肌增生等各项病理评分及病理总分,其中,对杯状细胞化生,炎症细胞浸润的作用在高剂量组更明显。氨茶碱对PEF无明显改善。结论:LTB4在COPD疾病中表达水平增高,参与气道炎症过程。氨茶碱的治疗可降低COPD大鼠BALF中LTB4水平以及中性粒细胞%,改善小气道病变。Objective ： To investigate the changes of leukotriene B4 （LTB4） in both the airways and the blood circulation in an animal model of chronic obstructive pulmonary disease （ COPD ） and the effects of theophylline on LTB4. Methods： Thirty-two male Wistar rats were divided into four groups by random number meter： Group A （ normal controls）, group B （ COPD）, group C （ smoking ＋ low dose theophylline）, and group D （smoking ＋ high dose theophylline ）, with 8 rats in each group. Pulmonary functions of the rats were assessed, and pathological changes of airways were scored. Cell counts and cell differentiation in bronchoalveolar lavage fluid （BALF） were also performed. Concentrations of IL-8 and LTB4 in BALF, plasma and lung tissue were measured by enzyme-linked immunosorbent assay （ELISA） and enzyme immunoassay （EIA）. Results： LTB4 concentrations in BALF of COPD rats increased significantly as compared with the normal controls, and positively correlated with the percentage of neutrophil and IL-8 in BALF （ r =0. 794,0. 863 ; P =0. 007,0.012 ）, and negatively correlated with peak expiratory flow （PEF） （r = -0. 718, P = 0.028 ）. Positive correlations were also found between levels of LTB4 in BALF and the scores of inflammatory cell infiltration of COPD rats （ r = 0. 836, P = 0. 036 ）. Treatment with theophylline decreased the percentage of neutrophil and the concentrations of LTtM in BALF of the COPD rats, attenuated the pathological changes of small airways, such as airway occlusion, gobletcell metaplasia, inflammatory cell infiltration, and fibrosis and smooth muscle proliferation. The effect was more significant on goblet-cell metaplasia and inflammatory cell infiltration in the high dose group. However theophylline had little effect on PEF. Conclusion： Our results suggest that LTB4 is involved in airway inflammation in COPD. Theophylline is effective in decreasing the levels of LTtM in BALF of COPD rats, reducing the percentage of neutrophil, and attenuat

关 键 词：白三烯B4 肺疾病 慢性阻塞性 疾病模型 动物 氨茶碱 

分 类 号：R563[医药卫生—呼吸系统]