正常肺组织急性重离子照射后基因标志物分析  

Transcriptional analysis of gene signatures in normal lung tissues after an acute exposure to heavy-ion irradiation

作　　者：耿继武[1] 周兆明 山常国 文磊 刘浩 成杰 周美娟 陈龙华[5] 蔡林波 周成 GENG Jiwu;ZHOU Zhaoming;SHAN Changguo;WEN Lei;LIU Hao;CHENG Jie;ZHOU Meijuan;CHEN Longhua;CAI Linbo;ZHOU Cheng(Guangdong Key Laboratory of Occupational Disease Prevention and Treatment/Guangdong Province Hospital for Occupational Disease Prevention and Treatment,Guangzhou 510300,China;Department of Radiation Oncology,Guangdong Sanjiu Brain Hospital,Guangzhou 510510,China;Department of Radiation Medicine,School of Public Health,Southern Medical University,Guangzhou 510515,China;Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;Department of Radiation Oncology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]广东省职业病防治院/广东省职业病防治重点实验室 [2]广东三九脑科医院肿瘤综合治疗科 [3]南方医科大学公共卫生学院放射医学系 [4]上海交通大学医学院附属仁济医院 [5]南方医科大学南方医院放疗科

出　　处：《中国医学物理学杂志》2019年第2期136-141,共6页Chinese Journal of Medical Physics

基　　金：国家自然科学青年科学基金(81703166)

摘　　要：目的:探索急性重离子辐射后早期差异表达的基因,以期查找出可提示重离子辐射的潜在基因标志物。方法:采用8～10周龄C57BL6雌性小鼠,随机分为照射组(12.5 Gy)和空白对照组(0 Gy),分组进行重离子全肺野照射或假照,于照射后2、24 h提取肺组织,借助基因芯片进行全基因组转录水平分析;予以实验动物梯度剂量照射,观察重离子敏感基因在照后第7天的量效关系。结果:小鼠肺组织经重离子照射后2 h,Trp53inp1、Phlda3、Ddit4l、Gtse1、Sesn2、Bbc3、Mdm2、Ptp4a1、Pmaip1与Osgin1等基因mRNA表达水平出现与辐射相关的显著增加;而同一时间点,Wisp2、IL33、Dido1、Efcab4a、Myo1f等5个基因显著下调。在照射后24 h,Phlda3、Ddit4l、Trp53inp1、Gtse1、Sesn2、Exoc4、Ephx1、Thyn1、Ei24等9个基因表达水平也出现了显著上升;而Gpihbp1、Sla、Hist1h3ah、Stc1、Cd2等5个基因则出现显著下调。急性期重离子辐射敏感基因在7 d梯度剂量照射实验被证实呈显著剂量依赖性上升趋势。结论:研究发现Trp53inp1、Phlda3、Sesn2、Gtse1与Ddit4l等5个可作为检测肺组织受到高线性能量传递射线辐射后发生应激反应的潜在基因标志物,这些应激反应辐射敏感基因仍有待在基因表达水平和蛋白水平的进一步验证。Objective To investigate the potential gene-signatures for normal tissue stress response after an acute exposure of heavyionirradiation in lung.Methods Female C57 BL6 mice aging 8-10 weeks old were randomly assigned into irradiation group(12.5 Gy)and non-irradiation group(0 Gy).The mice in irradiation group were exposure to heavy-ion irradiation,while those in nonirradiation group were exposure to sham irradiation.Gene chip was used to carry out genome-wide transcriptional analysis on lung tissues which were extracted at 2 and 24 hours after irradiation.Moreover,a dose-escalated irradiation was performed on mice to analyze the dose-effect relationship of heavy ion-sensitive genes at the 7^th day after irradiation.Results At 2 hours after irradiation,the m RNA expression levels of Trp53 inp1,Phlda3,Ddit4 l,Gtse1,Sesn2,Bbc3,Mdm2,Ptp4 a1,Pmaip1,and Osgin1 were found to be substantially up-regulated in mice lung tissues,while the mRNA expression levels of Wisp2,IL33,Dido1,Efcab4 a,and Myo1 f were apparently down-regulated.At 24 hours after irradiation,the expression levels of 9 genes,namely Phlda3,Ddit4l,Trp53 inp1,Gtse1,Sesn2,Exoc4,Ephx1,Thyn1 and Ei24 were increased remarkably,while the expression levels of Gpihbp1,Sla,and Hist1 h3 ah were obviously down-regulated.The most up-regulated gene-panel after acute exposure to heavyion irradiation was further validated by 7 days of dose-escalated irradiation.Conclusion Five genes,namely Trp53 inp1,Phlda3,Sesn2,Gtse1 and Ddit4 l,can be taken as the potential markers for detecting the stress response of lung tissues after high-linear energy transfer irradiation.Further investigations on PCR and protein levels are needed to substantiate these findings.

关 键 词：高能粒子射线 应激反应 放射性肺损伤 全基因组分析 生物标志物 

分 类 号：R312[医药卫生—基础医学] R146