卡托普利抗肺纤维化作用的实验研究

Anti-pulmonary Fibrosis Effect of Captopril in Rats

目的 :研究血管紧张肽转换酶 (ACE)抑制药卡托普利 (captopril,CPT)的抗肺纤维化作用及机制。方法 :3 0只SD大鼠随机分成治疗组、模型组和对照组各 10只 ,治疗组和模型组经气管内注入平阳霉素 (5mg·kg 1 ,0 .2～ 0 .3mL) ,当日开始经胃管内分别灌注CPT 60mg·kg 1 ·d 1 及 0 .9%氯化钠注射液 ,对照组气管内及胃管内均灌注 0 .9%氯化钠注射液。各组均于气管内灌药后第 7,2 8天各处死 5只 ,测动物体重及肺湿重 ,检测血清ACE活性 ,HE染色及HPIAS 10 0 0高清晰度彩色病理报告分析肺泡炎及肺纤维化程度 ,免疫组化测定 β1 转化生长因子 (TGF β1 )蛋白表达。结果 :治疗组肺泡炎及肺纤维化程度均轻于模型组 ,第 7天治疗组及模型组ACE活性明显高于对照组 (P <0 .0 1) ,第 2 8天模型组仍维持较高水平 ,治疗组第 7天TGF β1 明显低于模型组 ,第 2 8天 3组TGF β1 无显著差异。结论 :卡托普利通过抑制ACE活性 ,抑制TGF β1 的表达 ,具有抗肺泡炎、肺纤维化的作用。

Objective:To study the anti-pulmonary fibrosis effect of captopril (CPT) and its mechanism. Methods:Thirty SD rats were randomized into three groups: CPT-treated group, model group and control group evenly. The treatment group and the model group were intratracheally instilled with bleomycin (5 mg·kg -1, 0.2-0.3 mL), and the control group received sodium chloride injection. Then the treatment group fed with CPT, and the control fed with sodium chloride injection until they were killed. Five rats in each group were separately killed 7 d later and 28 d later for experimental check. Lung weights, ACE activity were tested. The degrees of lung alveolitis and pulmonary fibrosis were checked by hemotoxylin and eosin colouration, and by HPIAS image analysis. Transforming growth factor (TGF-β 1) was assessed by immunohistochemical technique. Results:The lung alveolitis and pulmonary fibrosis in the treatment group were significantly relieved by comparison to the model group. ACE activities in the treatment group were lower than in model group significantly 7 d later(P<0.01), and in model group, ACE activities still higher 28 d later. TGF-β 1 level in CPT-treated group was lower than model group 7 later, but there were no significant difference among the three groups 28 d later. Conclusion:Captopril has the effect of anti-pulmonary fibrosis in experimental rats by reducing ACE activity and inhibit expression of TGF-β 1.