卡托普利抗大鼠肺纤维化的作用及机制

目的探讨卡托普利对肺纤维化的治疗作用及可能的机制。方法将64只雄性SD大鼠随机分为对照组、博莱霉素模型组、卡托普利治疗组、地塞米松组治疗组，每组16只。采用HE染色、Masson染色行肺泡炎、肺纤维化程度分级，分别测定各组大鼠血浆AngⅡ、转化生长因子-β1（TGF-β1）mRNA含量以及羟脯氨酸、超氧化物歧化酶、丙二醛含量，并作各组间的对比分析。结果（1）第14天时：与对照组比较，其他3组大鼠肺泡炎评分、HYP含量、AngⅡ含量、MDA含量及TGF-β1 mRNA表达水平均明显升高（P〈0.05或0.01），SOD含量均显著降低（均P〈0.01），仅模型组肺纤维化评分显著高于对照组（P〈0.01）；与模型组比较，卡托普利组及地塞米松组肺泡炎、肺纤维化评分及HYP含量、AngⅡ含量、MDA含量及TGF-β1 mRNA表达水平均明显降低（P〈0.05或0.01），SOD含量均显著升高（均P〈0.01）；地塞米松组显著高于卡托普利组（P〈0.01），卡托普利组AngⅡ含量及TGF-β1 mRNA表达水平均明显低于地塞米松组（P〈0.05或0.01）。（2）第28天时：与对照组比较，其他3组大鼠肺泡炎及肺纤维化评分、HYP含量及TGF-β1 mRNA表达水平均显著升高（均P〈0.01），模型组和地塞米松组AngⅡ含量显著升高（均P〈0.01），仅模型组SOD含量显著降低、MDA含量显著升高（均P〈0.01）；与模型组比较，卡托普利组及地塞米松组肺泡炎及肺纤维化评分、HYP含量、MDA含量及TGF-β1 mRNA表达水平均明显低于模型组（均P〈0.05或0.01），SOD含量均显著升高（均P〈0.01），卡托普利组AngⅡ含量显著降低（P〈0.01），地塞米松组AngⅡ含量显著升高（P〈0.01）；卡托普利组TGF-β1 mRNA表达水平明显低于地塞米松组（P〈0.05）。结论卡托普利可能是通过抑制AngⅡ的生成、减少TGF-β1 mRNA的表达以及纠正氧化／抗氧化失衡而博莱霉素诱导的大鼠

The effect of captopril on pulmonary fibrosis of rats and its mechanism

Objective To investigate the effect of captopril on bleomycin-induced pulmonary fibrosis in rats and its mechanisms. Methods sixty-four male Sprague Dawley （SD） rats were randomly divided into four groups （n=16 in each group）： normal control group （group N）, bleomycin group （group M）, Captopril group （group K） and Dexamethasone group （group D）. The lung samples were taken for HE and Masson staining. Plasma levels of AngⅡ, Hydroxyproline （HYP）, SOD, MDA and TGF-β1 mRNA were also detected. Results Compared with group N,plasma levels of HYP,AngⅡ,MDA and TGF-β1 mRNA were higher （P 〈 0.05 or 0.01 ）and SOD levels were lower （P 〈 0.01 ）in three other groups at d14. Compared with group M, the alveolitis, pulmonary fibrosis were milder in group K and group D and plasma levels of HYP,AngⅡ,MDA and TGF-β1 mRNA （ P 〈 0.05 or 0.01 ）were lower and SOD levels were higher （ P 〈 0.01 ）. The levels of Angll and TGF-β1 mRNA in group K were lower than those in group D（ P 〈 0.05 or 0.01）. Compared with group N,the alveolitis, pulmonary fibrosis were more severe in three other groups and plasma levels of HYP, TGF-β1 mRNA were higher （P〈0.01）at d28. AngⅡ level was higher in group M and group D（ P〈 0.01 ）; SOD level was lower and MDA level was higher in group M（ P〈 0.01 ）. Compared with group M, group K and group D had milder alveolitis and pulmonary fibrosis, and lower HYP, MDA and TGF-β1 mRNA levels （P 〈 0.05 or 0.01 ）and higher level of SOD （ P〈0.01 ）. The level of AngⅡ was lower in group K and higher in group D（P〈0.01）. The level of TGF-β1 mRNA in group K was lower than that in group D （P〈 0.05）. Conclusion Captopril can alleviate pulmonary alveolitis and fibrosis in bleomycin-induced pulmonary fibrosis in rats, which are associated with decreased expression of AngⅡ and TGF-β1 and oxidation-antioxidation process.