布洛芬抑制博莱霉素诱导的肺纤维化小鼠一氧化氮生成的机制研究

 目的研究布洛芬对博莱霉素诱导的肺纤维化小鼠一氧化氮（NO）生成的影响及可能机制。方法通过气管内滴注博莱霉素复制小鼠肺纤维化模型，治疗组经腹腔注射给予不同剂量的布洛芬。用NO化学法试剂盒测定血清NO水平；用免疫组织化学法检测肺组织核因子-κB；用Westernblot法检测各组肺组织诱导性NO合成酶（iNOS）蛋白表达水平。结果与正常对照组比较，模型组血清NO水平、肺组织核因子κB（NF-κB）含量和iNOS的表达显著增加（P<0.01），布洛芬5mg/kg治疗组未见明显变化，而布洛芬10mg/kg和20mg/kg治疗组则明显降低（P<0.05，P<0.01）。布洛芬20mg/kg治疗组血清NO含量、肺组织NF-κB含量和iNOS的表达明显低于布洛芬5mg/kg和10mg/kg治疗组。结论布洛芬可抑制由博莱霉素引起的iNOS和NF-κB的上调，降低肺纤维化小鼠NO水平，可能是降低肺纤维化机制之一。

Effect of Ibuprofen on Nitric Oxide GenerationProduction in Bleomycin-pulmonary Fibrosis Mice

Objective To study the effect of ibuprofen on nitric oxide generation and explore possible mechanism in bleomycin-induced pulmonary fibrosis mice.Methods Pulmonary fibrosis mouse model were established by intratracheal instillation of bleomycin,and the treatment group received different doses of ibuprofen through intraperitoneal injection.Serum nitric oxide was analyzed using nitric oxide chemical method kit.Lung tissue nuclear factor-κB was detected by immunohistochemical method and inducible nitric oxide synthase in lung tissue was determined by Western blot.Results Compared with normal control group,serum nitric oxide,nuclear factor-κB and inducible nitric oxide synthase of lung tissue were significantly increased in model group (P<0.01).There was no significant difference in serum nitric oxide,nuclear factor-κB and inducible nitric oxide synthase of lung tissue between ibuprofen group (5 mg/kg) and normal control group.The increased serum nitric oxide,nuclear factor-κB and inducible nitric oxide synthase of lung tissue were alleviated in ibuprofen group (10 mg/kg) and ibuprofen group (20 mg/kg),significant differences were found compared with normal control group and ibuprofen group (5 mg/kg) (P<0.05 and P<0.01).Conclusion The present study showed that ibuprofen reduced bleomycin-induced up-regulation of nitric oxide,nuclear factor-κB,decreased level of serum nitric oxide,which partly explained the therapeutic mechanism of ibuprofen for pulmonary fibrosis.