小型猪右胸单次大剂量γ射线照射后的肺损伤研究  

The study on lung injury of minipigs＇ right-thorax with a single high-dose γ-ray irradiation

作　　者：岳海英[1] 胡凯[1] 蒋健[1] 陈玉华[2] 刘文其[1] 王仁生[1] 

机构地区：[1]广西医科大学第一附属医院放疗科,南宁530021 [2]广西壮族自治区妇幼保健院病理科

出　　处：《中华放射医学与防护杂志》2015年第8期561-565,共5页Chinese Journal of Radiological Medicine and Protection

基　　金：人口健康与食品安全关键技术研究开发基金（桂科攻1140003A-24）

摘　　要：目的 探讨巴马小型猪经右胸15 Gy的单次照射后肺泡Ⅱ型上皮细胞中细胞因子及蛋白的变化和可能的作用.方法 将40只雄性巴马小型猪按随机数字表法分为健康对照组（不予照射）和照射组（60Co γ射线进行右胸15 Gy单次照射）.照射后4、8、12、24周,从两组中分别取5只采集右侧肺组织,行HE染色观察肺组织病理变化;免疫组织化学染色观察α-平滑肌肌动蛋白（α-SMA蛋白）表达;免疫印迹检测肺表面活性物质相关蛋白A（SP-A）、转化生长因子β1（TGF-β1）、波形蛋白（Vimentin）和E-钙黏蛋白（E-cadherin）的蛋白表达;免疫荧光双染观察α-SMA和SP-A的共表达.结果 照射后的4、8、12和24周,照射组中α-SMA、TGF-β1和Vimentin的蛋白表达较健康对照组明显升高（α-SMA：t=2.46～3.26,P＜0.05;TGF-β1：t=2.96～3.52,P＜0.05;Vimentin：t=3.24 ～ 5.05,P＜0.05）;而SP-A和E-cadherin的蛋白表达低于健康对照组（SP-A：t =3.62 ～4.65,P ＜0.05;E-cadherin：t =2.53 ～4.15,P＜0.05）.照射后8周,照射组可见肺泡Ⅱ型上皮细胞的α-SMA和SP-A蛋白共染,而健康对照组中未见.结论 E-cadherin、TGF-β1和SP-A可以作为放射性肺损伤发生的预测指标,而肺泡Ⅱ型上皮细胞可通过向间质细胞转化参与放射性肺损伤的发生发展.Objective To explore the influence and mechanism of cytokines and protein expression of alveolar epithelial type （ACE） Ⅱ cells in Bama minipigs＇ right-thorax with a single 15 Gy dose irradiation.Methods All minipigs received either right thoracic irradiation or sham-irradiation under anesthesia.At 4,8,12 and 24 week post-irradiation,5 minipigs respective and random from irradiarion groups and control group were sacrificed to remove the lungs.The protein expression of surfactant associated protein （SP）-A,transforming growth factor （TGF）-β1,Vimentin and E-cadherin were detected by Western blot.The protein expression of α-smooth muscle actin （SMA） was detected by immunohistochemistry.The co-localization of SP-A and α-SMA was visualized by double immunofluorescence staining.Results At 4,8,12 and 24 week post-irradiation,a significant increase in the protein expression of α-SMA,TGF-β1 and Vimentin were observed in irradiated lung compared to sham-irradiated controls（α-SMA：t =2.46-3.26,P 〈0.05;TGF-β1：t =2.96-3.52,P 〈0.05;Vimentin：t =3.24-5.05,P 〈 0.05）.By contrast,the protein expression of SP-A and E-cadherin in irradiation group was lower than it in control group （SP-A：t =3.62-4.65,P 〈 0.05;E-cadherin：t =2.53-4.15,P 〈 0.05）.Moreover,at 8 week after irradiation,under confocal laser scanning microscope,the co-localization of SP-A and α-SMA was observed in irradiated alveolar epithelium cells,and it was not observed in sham-irradiated controls.Conclusions These data demonstrate that E-cadherin,SP-A and TGF-β1 may act as sensitive predictors of radiation-induced lung injury（RILI）.Irradiation may lead to ACE Ⅱ cells achieving a mesenchymal phenotype,namely,epithelial to mesenchymal cells transition occurs,and ACE Ⅱ cells play the important part in the development of RILI by epithelial-mesenchymal transition.

关 键 词：放疗 小型猪 肺泡Ⅱ型上皮细胞 上皮细胞向间质细胞转化 

分 类 号：R730.55[医药卫生—肿瘤]