二甲双胍对博来霉素诱导大鼠肺纤维化的影响*

Therapeutic effect of Metformin on Bleomycin induced pulmonary fibrosis in rats*

摘要:

目的 探讨二甲双胍对博来霉素诱导的中晚期肺纤维化的治疗效果。方法 将44只SD雄性大鼠分为5组。空白对照组4只，模型复制成功的24只又随机分为模型组、二甲双胍组、泼尼松组及吡非尼酮组，每组6只。除空白对照组外（予以气管内注射生理盐水1?ml/kg），其余各组予以气管内单次注入博来霉素5?mg/kg以复制肺纤维化模型，模型复制14?d后再予以相应药物干预，用药14?d后处死大鼠取材。采用HE染色和Masson染色观察肺组织病理变化。通过ELISA检测肺组织匀浆液、肺泡灌洗液中转化生长因子β（TGF-β）及羟脯氨酸（Hyp）的含量。结果 通过气管内单次注射博来霉素能够诱导大鼠肺纤维化。二甲双胍、吡非尼酮在一定程度上能减轻由博来霉素所诱导的肺部炎症及肺纤维化。二甲双胍、吡非尼酮可抑制TGF-β、Hyp的产生，且二甲双胍与吡非尼酮比较差异无统计学意义（P?>0.05）。泼尼松对中晚期肺纤维化无治疗作用。结论 二甲双胍、吡非尼酮可缓解由博来霉素所诱导的中晚期大鼠肺纤维化。泼尼松对博来霉素所诱导的中晚期大鼠肺纤维化无治疗作用。

Abstract:

Objective To investigate the therapeutic effect of Metformin on Bleomycin induced pulmonary fibrosis. Methods Rat model of pulmonary fibrosis was established by inhalation of Bleomycin (with 24 successful rats model). Rats in control group (4 rats) received normal saline. Rats were administrated with Metformin, Prednisone or Pirfenidone 14 days after insults (6 for each group). No treatment was applied to rats in model group (6 rats). The pathological changes of lung tissue were observed by HE staining and Masson staining. Levels of TGF-beta and Hyp in bronchoalveolar lavage fluid and lung tissue were determined by ELISA. Results Rat model of Bleomycin induced pulmonary fibrosis was established successfully. HE staining and Masson staining suggested that Bleomycin induced pulmonary inflammation and fibrosis were mitigated by Metformin and Pirfenidone. Metformin and Pirfenidone inhibited the production of Hyp and TGF-beta. Prednisone exerted no obvious therapeutic effect on pulmonary fibrosis in late stage. Conclusions Metformin and Pirfenidone excluding Prednisone relieve advanced pulmonary fibrosis.