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

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

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(NF-κB);用Western blot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、NF-κB含量和iNOS的表达显著增加(P<0.01),布洛芬5 mg/kg治疗组未见明显变化,而布洛芬10 mg/kg和20 mg/kg治疗组则明显降低(P<0.05,P<0.01)。布洛芬20 mg/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5 mg/kg和10 mg/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。

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 was established by intratraeheal instillation of bleomycin, and the treat- ment 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 Westem 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 ox- ide,nuclear faetor-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 faetor-κB and inducible nitric oxide synthase of lung tissue were alleviated in ibuprofen group （10 mg/kg ） and ibuprefen 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.