| 王晔,熊咏超,薛少博,吴志华,彭振军.二甲双胍对大鼠放射性肺纤维化的防治作用机制[J].中华放射医学与防护杂志,2017,37(10):736-741 |
| 二甲双胍对大鼠放射性肺纤维化的防治作用机制 |
| Attenuation of metformin on radiation-induced lung fibrosis in rats |
| 投稿时间：2017-03-14 |
| DOI：10.3760/cma.j.issn.0254-5098.2017.10.003 |
| 中文关键词: 二甲双胍 放射性肺损伤 转化生长因子β 纤维化 |
| 英文关键词:Metformin Radiation-induced pulmonary injury Transforming growth factor-β Fibrosis |
| 基金项目:湖北省自然科学基金（2017CFB770） |
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| 中文摘要: |
| 目的 探讨二甲双胍对大鼠放射性肺纤维化的防治效果及机制。方法 将30只成年Sprague-Dawley（SD）大鼠按随机数字表法分为3组：对照组、单纯照射组和照射联合二甲双胍组，每组10只。采用6 MV X射线，对大鼠右侧肺照射20 Gy。在观察期间测定CT值。在放疗后第12周，取肺组织进行HE染色、Masson染色和天狼星染色，检测肺组织的纤维化及炎症标的相关蛋白表达。非小细胞肺癌（NSCLC）A549和H460细胞经5 mmol/L二甲双胍或PBS预处理24 h后，分别暴露于0和2 Gy的X射线。CCK-8检测细胞活性。结果 在大鼠模型中，与单纯照射组比较，二甲双胍可显著减轻由于射线造成的影像学和组织学的纤维化表现以及肺密度（6.52±0.43 vs. 3.31±0.57，t=6.37， P<0.01）和羟脯氨酸含量的增加（32.58±1.59 vs. 23.47±2.46，t=12.72， P<0.01）。同时，与单纯照射组相比，其明显降低I型胶原蛋白、p-AMPKα和TGF-β的表达，并抑制p-Smad2和p-Smad3表达。此外，二甲双胍以剂量依赖的方式抑制A549和H460细胞的活性。结论 二甲双胍对射线诱发的肺纤维化具有保护作用，其可以被用作放射防护剂。 |
| 英文摘要: |
| Objective To evaluate the radioprotective effects of metformin on radiation-induced pulmonary injury in rats.Method A total of 30 Sprague-Dawley (SD) rats were randomly divided into three groups:control, radiation (20 Gy) and radiation (20 Gy) with metformin, with 10 rats in each group. The right lungs of rats were irradiated to 20 Gy with 6 MV X-rays. Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. The tissue samples of lung were extracted to perform the histological analysis, measurement of hydroxyproline content, fibrosis score and evaluation of fibrosis/inflammatory markers by Western blot at 12 weeks post-irradiation. CCK-8 method was used to explore the effects of metformin on non-small cell lung cancer(NSCLC) cells A549 and H460.Results Metformin reduced radiologic and histologic signs of fibrosis, lung density(6.52±0.43 vs. 3.31±0.57,t=6.37, P<0.01)and hydroxyproline content(32.58±1.59 vs. 23.47±2.46,t=12.72, P<0.01)which had been increased due to irradiation. Meanwhile, it significantly decreased the expressions of Col1, p-AMPKα and TGF-β, while inhibited the expressions of p-Smad2 and p-Smad3 compared to the irradiation alone group. Moreover, metformin reduced A549 and H460 cells growth.Conclusions Metformin exerted a protective effect on normal tissues in radiation-induced pulmonary fibrosis. Thus, it might act as a promising radioprotective agent in the treatment of lung cancer. |
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