摘要
目的通过Smad3特异性抑制剂(specific inhibitor of Smad3,SIS3)干预博来霉素肺纤维化大鼠,观察转化生长因子β1(TGF-β1)、Smad3蛋白表达情况,探讨TGF-β1/Smad3信号通路在肺纤维化中的作用。方法选取健康成年雄性SD大鼠60只,随机分为4组:生理盐水对照组(NS组),博来霉素组(BLM组),SIS3干预组(SIS3组),二甲基亚砜溶媒组(DMSO组),每组15只。BLM组、SIS3组和DMSO组气管内注射博来霉素溶液(5mg/kg)建立大鼠肺纤维化模型;NS组以同样方法注入等量生理盐水;SIS3组大鼠腹腔内注射SIS3(2.5μg/g)干预处理,BLM组注射等量生理盐水,DMSO组注射等量DMSO。各组于造模后第7、14、28天分别处死5只大鼠,行Masson染色观察各组肺组织胶原纤维差异。免疫组化检测各组TGF-β1、Smad3表达情况。结果与NS组比较,BLM组、DMSO组大鼠肺组织出现明显纤维化,TGF-β1、Smad3表达明显增高;与BLM组、DMSO组相比,SIS3组大鼠肺纤维化程度减轻,TGF-β1、Smad3表达减少。结论 SIS3干预肺纤维化大鼠,能够减轻大鼠肺泡炎,降低肺纤维化程度;TGF-β1/Smad3信号通路在肺纤维化中可能起到重要作用。
Objective To observe the expressions of transforming growth factor-β1（TGF-β1）and Smad3 protein in rats with bleomycin-induced pulmonary fibrosis via the intervention of specific inhibitor of Smad3（SIS3）and explore the role of TGF-β1/Smad3 signaling pathway in pulmonary fibrosis.Methods Sixty male SD rats were randomly divided into four groups including the normal saline control group（NS group）,bleomycin group（BLM group）,SIS3 intervention group（SIS3group）,and dimethyl sulfoxide（DMSO group）,and each group consisted of 15 rats.The rats in the BLM,SIS3 and DMSO groups were given intratracheal injection with bleomycin solution（5 mg/kg）to establish the rat models with pulmonary fibrosis,while the rats in the NS group was injected with the same amount of normal saline.The rats in the SIS3 group were injected intraperitoneally with SIS3（2.5μg/g）,those in the BLM group were injected with the same amount of normal saline,and those in the DMSO group were injected with the same amount of dimethyl sulfoxide.Five rats of each group were sacrificed on the 7th,14 th and 28 th day after the modeling.The Masson staining was applied to observe the differences of collagen fibers in lung tissues,and the immunohistochemical staining was adopted to detect the expressions of TGF-β1,Smad3 in each group.Results Compared with the NS group,the lung tissues of the BLM and DMSO groups showed significant fibrosis and the expressions of TGF-β1and Smad3 were significantly increased.Compared with the BLM and DMSO groups,the degree of pulmonary fibrosis were decreased in the SIS3 group and the expressions of TGF-β1and Smad3 were decreased.Conclusion Firstly,SIS3 can alleviate alveolitis and reduce the pulmonary fibrosis in rats with pulmonary fibrosis.Secondly,the TGF-β1/Smad3 signaling pathway may play an important role in pulmonary fibrosis.
出处
《成都医学院学报》
CAS
2017年第3期271-276,共6页
Journal of Chengdu Medical College
