COPD大鼠肺组织中LTB4水平、5-LO mRNA表达及齐留通的干预作用

Effect of Zileuton on Expression of 5-lipoxygenase mRNA and LTB4 in Chronic Obstructive Pulmonary Disease Rats

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。

Objective To observe the relationship between leukotriene B4 （ LTB4 ） ,5-1ipoxygenase（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 23 days, then the lung function of rats were as- sessed, 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, FEV0. 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 ： FEV0. 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.