血管紧张素转化酶抑制剂对博来霉素诱导肺纤维化大鼠肺功能改变的影响

Effect of angiotensin-converting enzyme inhibitor on pulmonary fibrosis changes of lung function in rats

目的探讨血管紧张素转化酶抑制剂(ACEI)对博来霉素诱导肺纤维化大鼠肺功能改变的影响。方法在博来霉素诱导肺纤维化大鼠模型的基础上,采用卡托普利对肺纤维化大鼠进行干预。检测大鼠肺泡炎、肺纤维化半定量评分,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、IL-6水平,肺组织匀浆中过氧化物歧化酶(SOD)、丙二醛(MDA)及肺组织羟脯氨酸(HYP)水平,BALF和血清中基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂(TIMP-1)水平,并在显微镜下观察大鼠肺组织形态学改变。结果卡托普利可显著减轻博来霉素诱导的肺纤维化大鼠的肺纤维化评分,升高BALF中TGF-β1水平,并降低INF-γ、IL-1、IL-2、IL-4、IL-6水平;肺组织匀浆SOD水平升高,MDA及HYP水平降低;血清及BALF中MMP-9、TIMP-1均呈降低趋势,镜下观察肺纤维化明显减轻。结论卡托普利对博来霉素诱导肺纤维化大鼠的肺功能下降有明显的抑制作用。

Objective To investigate the effect of angiotensin-converting enzyme inhibitor （ACEI） on lung function changes of pulmonary fibrosis induced by bleomycin in rats. Methods Based on the pulmonary fibrosis models in rats induced by bleomycin, the semiquantitative score of rat alveolar inflammation and lung fibrosis were detected after the intervention of captopril which was ACEI. The content of transforming growth factor-131 （ TGF-131 ）, interferon-γ（ INF-γ）, intedeukin （IL） -1, IL-2, IL-4, IL-6 in bronchoalveolar lavage fluid （ BALF）, the content of superoxide dismutase （ SOD）, malondialdehyde （MDA） and hydroxyproline （HYP） in pulmonary tissue homogenate, the content of matrix metalloprote-inases-9 （MMP-9）, tissue inhib- itor of metalloproteinase-1 （TIMP-I） in BALF and blood serum were detected. The lung histomorphology was observed under microscope. Results Captopril reduced the scores of rat alveolar inflammation and lung fibrosis,increased the TGF-β1 and the INF-γ, IL-1, IL-2, IL-4, IL-6 content in BALF, increased the SOD and reduced the MDA, HYP content in pulmonary tissue ho- mogenate,reduced the MMP-9 and TIMP-1 content in BALF and blood serum. The degree of pulmonary fibrosis under micro- scope was significantly reduced. Conclusion Captopril can effectively inhibit the pulmonary fibrosis in rats induced by bleo- mycin.