依那普利对博来霉素致大鼠肺纤维化的影响

Effect of enalapril on pulmonary fibrosis induced by bleomycin in rats

目的探讨依那普利对博来霉素致肺纤维化大鼠肺组织中细胞因子和肺纤维化的影响。方法 60只Wistar大鼠随机分为正常对照组、模型组、低剂量依那普利组、中剂量依那普利组、高剂量依那普利组和泼尼松对照组,每组10只。博来霉素诱导大鼠肺纤维化模型。对各组大鼠进行肺泡炎、肺纤维化半定量评分,检测支气管肺泡灌洗液(BALF)中转化生长因子-β1(TGF-β1)、干扰素-γ(INF-γ)、白细胞介素(IL)-1、IL-2、IL-4和IL-6含量,肺组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)和羟脯氨酸(HYP)含量,BALF和血清中间质金属蛋白酶(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)的浓度,以及肺组织中肿瘤坏死因子-α(TNF-α)m-RNA的表达。结果依那普利剂量依赖性地降低博来霉素诱导的肺纤维化大鼠的肺纤维化评分和肺泡炎评分(P<0.05);降低大鼠BALF中TGF-β1、IL-1、IL-2、IL-4、IL-6的含量(P<0.05),并升高INF-γ含量(P<0.05);升高肺组织中SOD含量(P<0.05),并降低MDA和HYP含量(P<0.05);降低血清及BLAF中MMP-9、TMP-1的含量,降低MMP-9/TMP-1值(P<0.05);降低肺组织TNF-αm-RNA的表达(P<0.05)。结论依那普利可以有效抑制博来霉素诱导的大鼠肺纤维化。

Objective To explore the effect of enalapril on pulmonary fibrosis and cell factors in rats with pulmonary fibrosis induced by bleomycin.Methods Sixty Wistar rats were randomly divided into normal control group,model group,low-dose enalapril group,medium-dose enalapril group,high-dose enalapril group and prednisone group,ten rats in each group.The pulmonary fibrosis models were induced by bleomycin in rats.The semiquantitative score of airsacculitis and lung fibrosis,the contents of transforming growth factor-β1（TGF-β1）,interferon-γ（INF-γ）,interleukin（IL）-1,IL-2,IL-4,IL-6 in bronchoalveolar lavage fluid（BALF）,the contents of interleukin（SOD）,malondialdehyde（MDA） and hydroxyproline（HYP） in pulmonary tissue homogenate,the contents of matrix metalloproteinases-9（MMP-9）,tissue inhibitor of metalloproteinase-1（TIMP-1） in BALF and serum,and the expression of TNF-α m-RNA in lung tissue were detected in each group.Results Enalapril dose-dependently reduced the scores of pulmonary fibrosis and airsacculitis in rats with pulmonary fibrosis induced by bleomycin（P0.05）,and reduced the contents of TGF-β1,IL-1,IL-2,IL-4 and IL-6 in BALF（P0.05）,increased the contents of INF-γ in BALF and SOD in pulmonary tissue（P0.05）,reduced the contents of MDA and HYP in pulmonary tissue（P0.05）,reduced the contents of MMP-9 and TMP-1 in BALF and serum（P0.05）,reduced the ratio of MMP-9 and TMP-1（P0.05）,reduced the expression of TNF-α m-RNA in pulmonary tissue（P0.05）.Conclusion Enalapril can effectively inhibit the pulmonary fibrosis induced by bleomycin in rats.