【摘要】 目的探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠模型肺组织中白三烯B4(LeukotrieneB4,LTB4)含量与5-脂氧合酶(5-LO,5-lipoxygenase)mRNA水平的变化,以及给予齐留通干预的影响。方法 36只健康雄性Wistar大鼠随机分为对照组、模型组、药物组,采用被动吸烟法制作COPD大鼠模型,给予药物组鼻饲齐留通,测定肺功能,各组肺组织匀浆检测其LTB4含量及髓过氧化物酶(Myeloperoxidase,MPO)活性,RT-PCR法检测5-LO mRAN的表达。结果模型组、药物组的0.3秒用力呼吸容积(Forced expiratory volume in the 0.3 second,FEV0.3)/用力肺活量(Forced vital capacity,FVC)%较对照组显著下降(P<0.001),吸气相阻力(Inspiratory phase resistance,Ri)和呼气相阻力(expiratory phase resistance,Re)较对照组显著增加(P<0.001,P<0.05);模型组较药物组FEV0.3/FVC%下降程度更低,Ri、Re更高,两纽间差异有显著性(P<0.05)。比较各纽大鼠肺纽织LTB4水平,MPO活性及5-LOmRNA表达:模型组、药物组较对照组显著升高(P<0.001);与模型组比较,齐留通干预使得三项指标均有显著降低(P<0.001)。结论 LTB4及5-LO参与COPD的气道炎症过程。5-LOX抑制剂齐留通可部分抑制减少COPD大鼠肺组织中LTB4产生,其机制可能为抑制5-LO表达。更多还原

【Abstract】 Objective To observe the relationship between leukotriene B4(LTB4),5-lipoxygenase(5-LO) and chronic obstructive pulmonary disease(COPD) and to evaluate the efficacy of 5-LOX inhibitor,zileuton on COPD rats.Methods Male Wistar rats were randomly divided into three groups of control(normal),model(COPD),and drug treatment(COPD + zileuton),with 12 rats in each group.Rat models were made by being smoked.The rats of drug group were treated with zileuton 50mg/kg everyday for 23days,then the lung function of rats were assessed, the contents of LTB4 and MPO of lung were checked by ELISA.The 5-LO mRNA expression were studied by reverse transcription polymerase chain reaction(RT-PCR).Results Compared with control group,FEVO.3/FVC%in COPD rats was declined obviously(P<0.001 ),while the Ri and Re were increased obviously(P<0.001 and P<0.05 Respectively).Levels of LTB4 and MPO,5-LO mRNA expression in the COPD rats were increased obviously(P<0.001 ).Compared with the model group:FE V0.3/FVC%in the drug group was declined moderately(P>0.05),Ri and Re of the drug group were increased moderately(P>0.05);the levels of LTB4,MPO and 5-LO mRNA expression were obviously declined by treated with zileton(P<0.001 ).Conclusion Those results suggest that LTB4 and 5-LO are involved in airway inflammation of COPD.Zileuton inhibits pulmonary inflammatory of COPD,which might be related to the reduction of LTB4 through 5-LO pathway.更多还原