布洛芬对小鼠肺纤维化的保护作用  

Experimental Study of Protective Effect of Ibuprofen on the Pulmonary Fibrosis in Mice

作　　者：王春雷[1] 张钰淼 张烨[1] 

机构地区：[1]中国医科大学附属第一医院老年病科,沈阳110001

出　　处：《中国医科大学学报》2012年第8期696-699,共4页Journal of China Medical University

基　　金：辽宁省教育厅高校科研计划(2010686)

摘　　要：目的研究布洛芬对博莱霉素诱导的肺纤维化的治疗保护作用。方法通过气管内滴注博莱霉素复制小鼠肺纤维化模型,实验分为正常对照组、模型组、布洛芬5 mg/kg治疗组、布洛芬10 mg/kg治疗组和布洛芬20 mg/kg治疗组。采集血清行一氧化氮(NO)化学法检测小鼠血清中NO含量;收集肺泡灌洗液行ELISA方法测定肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)含量;留取肺组织行HE染色观察各组小鼠肺组织形态变化,制备肺组织匀浆测定匀浆中丙二醛(MDA)含量;采用RT-PCR和Western blot检测肺组织中转化生长因子β1(TGF-β1)、Smad2和p-Smad2的表达水平。结果与正常对照组比较,肺纤维化模型组肺组织中发生炎性细胞浸润、肺泡间隔增厚情况,同时血清中NO含量和肺泡灌洗液中炎性因子TNF-α和IL-6含量显著增加,小鼠肺组织中MDA含量也有所增加,TGF-β1和p-Smad2的表达显著升高。经布洛芬治疗后,各项生化指标有所下降,同时肺纤维化损伤得以缓解。结论布洛芬可缓解由博莱霉素诱导的肺纤维化,其作用机制可能与下调NO含量、TNF-α和IL-6等炎性因子含量及调控TGF-β信号通路有关。Objective To study the protective effect of ibuprofen on bleomycin-induced pulmonary fthmsis. Methods The pulmonary fi- brosis mouse model was established by intratracheal instillation of bleomycin. The experimental mice were divided into normal control group, model group,5 mg/kg brufen treated group,10 mg/kg brufen treated group,and 20 mg/kg brufen treated group. Serum was collected to detect the content of NO by NO chemical method; lavage fluid was collected for determination of TNF-ct and IL-6 levels by using ELISA ; specimens of lung tissue were stained with HE to observe the morphological changes, and lung homogenates were prepared for determination of malondi- aldehyde （MDA）;the expression levels TGF-β1 ,Smad2 and p-Smad2 in hmg tissue were detected by RT-PCR and Western blot analysis. Resldts Compared with the normal control group, inflammatory cell infdtration, alveolar septal thickening occurred in lung tissue of pul- monary fibrosis model;meanwhile,NO content in serum and inflammatory cytokines TNF-αand IL-6 levels in bmnchoalveolar lavage fluid were significantly increased, MDA content was also increased in the lung tissue of mice, the expressions of TGF-β1 and p-Smad2 were signifi- candy increased;after ibupmfen administration,various biochemical indicators declined, and pulmonary fibrosis damage was mitigated. Con- clusion Ibuprofen can alleviated bleomycin-induced pttlrnonary fibrosis,and the mechanism may be associated with lowered content of NO, TNF-α, IL-6 and other inflammatory eytokines content and regulation of TGF-β signaling pathway.

关 键 词：布洛芬 博莱霉素 肺纤维化 

分 类 号：R743.5[医药卫生—神经病学与精神病学]