卡托普利对博莱霉素致小鼠肺纤维化的防治作用及其机制探讨  

Effect of captopril on bleomycin-induced pulmonary fibrosis in mouse

作　　者：彭张哲[1] 朱玉娴[2] 陶立坚[1] 王菱[1] 宁旺斌[1] 

机构地区：[1]中南大学湘雅医院肾内科,湖南长沙410078 [2]中国人民解放军第二军医大学长征医院肾内科,中国上海200003

出　　处：《中国现代医学杂志》2010年第4期539-543,共5页China Journal of Modern Medicine

摘　　要：目的研究血管紧张素转化酶抑制剂卡托普利对博莱霉素致小鼠肺纤维化的防治作用。方法7～10周龄雄性ICR小鼠45只分3组,分别为模型组、卡托普利组与正常对照组。模型组与卡托普利组经尾静脉注射博莱霉素10mg/(kg·d)14d建立稳定的肺间质纤维化模型,卡托普利治疗组于注射博莱霉素前24h予卡托普利(12.5mg/kg·d)灌胃,并与正常ICR小鼠进行对照。第28天收获肺组织,左肺行HE和Masson染色,右肺组织应用Real-time PCR检测CollagenⅠ、CollagenⅢ、TGFβ1及结缔组织生长因子CTGF mRNA表达,行Western-blot检测CTGF蛋白表达。结果卡托普利治疗组与模型组比较,小鼠肺泡炎、纤维化程度有所改善,但无统计学意义。卡托普利能显著下调模型组肺组织中升高的CollagenⅠ、TGFβ1的mRNA水平及CTGF的mRNA与蛋白水平,但Collagen Ⅲ的mRNA水平并无明显改变。结论卡托普利有减轻BLM诱导的肺泡炎及肺纤维化程度的趋势,提示卡托普利有一定的抗肺间质纤维化作用;抑制TGF-β1及CTGF在肺组织中的表达,可能是其作用机制之一。：【Objective】To explore the curative effects of captopril on lung fibrosis in murine bleomycin（BLM）-induced pulmonary fibrosis. 【Methods】Male ICR mice were intravenously injected with BLM 10mg/（kg·d） or saline （SA）. Captopril （12.5 mg/kg·d） was administered through stomach 1 day before commencement of BLM or SA, and continued throughout the course of the experiment. The 45 mice aged 7-10 weeks were randomly divided into three experimental groups： ①BLM-treated with SA group; ②BLM-treated with captopril group; ③SA-treated group. On the 28th day, lung tissues were collected. Sections of the left lung tissue were stained with HE and Masson staining; and the right lung tissue was used for both real-time PCR to detect the expression of Collagen Ⅰ, Collagen Ⅲ, TGFβ1 and CTGF mRNA, and Western blot to examine the expression of CTGF. 【Results】Captopril group showed a slight reduction of fibrotic lesions compared with the corresponding BLM group （P 0.05）. Western-blot and realtime PCR studies showed that BLM treatment significantly increased the mRNA level of Collagen Ⅰ, Collagen Ⅲ, TGFβ1 and CTGF. Treatment with captopril significantly reduced the over-expression of Collagen I, TGFβ1 and CTGF mRNA but not Collagen Ⅲ mRNA. 【Conclusion】Captopril could attenuate accumulation and deposition of extracellular matrix seen in pulmonary fibrosis and also block the expression of TGFβ1 and CTGF in murine bleomycin-induced pulmonary fibrosis.

关 键 词：肺纤维化 卡托普利 博莱霉素 转化生长因子Β1 结缔组织生长因子 

分 类 号：R563[医药卫生—呼吸系统]