摘要
目的 研究LY2109761对小鼠放射性肺纤维化的防治作用及机制，为放射性肺纤维的临床治疗提供参考。方法 选取8周龄、雌性、体重为18~22 g的C57BL/6小鼠40只，将小鼠按随机数表法分为空白对照组、单纯照射组、照射＋LY 50组和照射＋LY100组，每组10只，建立放射性肺损伤小鼠模型。空白对照组为假照射；单纯照射组给予6 MVX射线12 Gy单次照射全肺；照射＋LY50组和照射＋LY100组为照射后分别给予50和100 mg/kg LY2109761，分2次灌胃。于照射后2周分别对各组小鼠肺组织进行检测：HE染色后镜下观察肺组织病理形态，Masson染色观察肺组织的纤维化程度，免疫组织化学法测定肺内TGF-β1和Smad2的表达水平。结果 通过病理改变及评分，单纯照射组与空白对照组比较，放射后第14天肺泡结构发生变化，成纤维细胞增生；肺泡间隔明显增宽，可见片状的纤维化改变，肺纤维化表现明显。照射＋LY100组与单纯照射组比较，放射性肺纤维化程度明显减轻，差异有统计学意义（t=4.668，P〈0.05），而照射＋LY50组与单纯照射组比较，差异无统计学意义（P〉0.05）。免疫组织化学检测提示，TGF-β1及Smad2蛋白的表达水平单纯照射组与空白对照组比较，明显升高，差异具有统计学意义（t=13.545、6.418，P〈0.05），而照射＋LY100组与单纯照射组比较，其表达水平有明显降低，差异有统计学意义（t=15.263、6.855，P〈0.05），照射＋LY50组与单纯照射组比较，差异无统计学意义（P〉0.05）。结论 LY2109761对放射性肺纤维化有治疗作用且可能具有剂量依赖，其机制可能是通过抑制TGF-β1/Smad2通路来实现的。
Objective To investigate the protective effects and mechanism of LY2109761 in radiation-induced pulmonary fibrosis （RIPF）, and to provide a clue for the clinical treatment of RIPF.Methods A total of 40 healthy female C57BL/6 mice were enrolled and were divided into 4 groups with 10 mice in each group randomly, including blank control group, single irradiation group, irradiation＋LY50 group and irradiation＋LY100 group which were given 50 and 100 mg/kg of LY2109761 respectively, twice per day. The whole lungs were irradiated by 6 MV X-rays of 12 Gy. At 2 weeks post-irradiation, pathological analyses were performed for each group to evaluate the histological changes in the irradiated lungs, including hematoxylin and eosin staining （HE） to observe morphologic changes, the Masson staining to estimate the degree of fibrosis and a combination of immunohistochemistry to analyze the expression levels of TGF-β1 and Smad2.Results Compared with control group, the degree of fibrosis of the lung including alveolar structure changes, fibroblast proliferation and alveolar spacing was significantly enhanced at 14 d post-irradiation. Compared with irradiation group, the fibrosis degree in irradiation＋LY100 group was significantly reduced（t=4.668,P〈0.05）. The degree of inflammation and fibrosis of the lung in irradiation＋LY50 didn＇t obviously reduce compared with irradiation group （P〉0.05）. The result of immunohistochemical assay showed that, the level of protein expressions of TGF-β1 and Smad2 was increased significantly after irradiation（t=13.545, 6.418, P〈0.05）, and obviously decreased in irradiation＋LY100 group （t=15.263, 6.855, P〈0.05）, but just slightly reduced in irradiation＋LY50 group （P〉0.05）.Conclusions LY2109761 has protective effect in radiation pulmonary fibrosis possibly by down regulating the expressions of TGF-β1/Smad2.
出处
《中华放射医学与防护杂志》
CAS
CSCD
北大核心
2017年第9期651-655,共5页
Chinese Journal of Radiological Medicine and Protection
