大鼠WBI后海马区NFATc4／3信号通路相关因子改变的研究  

The change of NFATc4/3 signaling pathway in the rat hippocampus following whole brain irradiation

作　　者：陈清清[1] 周梦耘 孙锐[1] 张奇贤[1] 曹毅[3] 田野[1,2] 

机构地区：[1]苏州大学附属第二医院放疗科,215004 [2]苏州大学放射肿瘤治疗学研究所 苏州市肿瘤放疗学重点实验室 [3]苏州大学医学部公共卫生学院

出　　处：《中华放射肿瘤学杂志》2017年第1期79-83,共5页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金（81372411,81172128）;江苏省临床医学科技专项资助项目（BL2014040）;苏州市科技发展计划项目（SZS201509）

摘　　要：目的 探讨SD大鼠WBI后海马区NFATc4/3信号通路相关因子的改变。方法 将120只1个月龄雄性SD大鼠随机分为5个组,采用4 MeV电子线进行0、2、10、20 Gy单次WBI,在照射后6 h、12 h、1 d、3 d、1周、2周,用蛋白印迹法和RT-PCR方法检测海马区CaN、NFATc4/3、p-NFATc4/3、GSK-3β表达量变化。结果 照射后6、12 hNFATc4/3、p-NFATc4/3表达无变化,照射后1 d随照射剂量增加p-NFATc4/3表达水平与0 Gy相比明显升高（2 GyP=0.014、10 GyP=0.011、20 GyP=0.000）,而NFATc4/3的表达水平无变化;照射后3 d、1周和2周NFATc4/3表达水平与0 Gy相比显著下降（3 d 2 GyP=0.040、10 GyP=0.000、20 GyP=0.000、1周2 GyP=0.692、10 GyP=0.032、20 GyP=0.021、2周2 GyP=0.001、10 GyP=0.000、20 GyP=0.000）,而p-NFATc4/3表达均无变化。各剂量组间CaN、GSK-3β的表达未随照射时间、剂量变化而变化。结论 电离辐射对海马NFATc4/3信号通路有抑制作用,推测放射性认知功能障碍可能与NFATc4/3信号通路相关。Objective This study is to investigate the changes in the NFATc4/3 signaling pathway in rat hippocampus after whole brain radiation. Methods A total of 120 one-month-old male Sprague-Dawley rats were randomly divided into four groups to receive whole brain radiation using 4-MeV electron beams with doses of 0（control）,2,10,and 20 Gy,respectively,in a single fraction. At 6 hours,12 hours,1 day,3 days,1 week,and 2 weeks after radiation,Western blot and real-time PCR were used to evaluate the changes in expression levels of CaN,NFATc4/3,p-NFATc4/3,and GSK-3β. Results There were no significant changes in the expression of NFATc4/3 or p-NFATc4/3 at 6 and 12 hours after whole brain radiation. At 1 day after radiation,compared with the control group,the expression of p-NFATc4/3 in the radiation groups was significantly increased in a dose-dependent manner （2 Gy：P=0.014;10 Gy：P=0.011;20 Gy：P=0.000）;however,there was no significant difference in the expression of NFATc4/3 between the radiation group and the control group. The expression of NFATc4/3 was significantly decreased in the radiation groups than in the control group at day 3（2 Gy：P=0.040;10 Gy：P=0.000;20 Gy：P=0.000）,1 week （2 Gy：P=0.692;10 Gy：P=0.032;20 Gy：P=0.021）,and 2 weeks （2 Gy：P=0.001;10 Gy：P=0.000;20 Gy：P=0.000） after radiation,while there was no significant difference in the expression of p-NFATc4/3 between any two groups. There were no time-or dose-dependent changes in expression of CaN or GSK-3β. Conclusions Ionization radiation has an inhibitory effect on the NFATc4/3 signaling pathway in rat hippocampus. Combined with our previous results,this study suggests that radiation-induced cognitive dysfunction is associated with the NFATc4/3 signaling pathway.

关 键 词：全脑照射 NFATC 4/3基因 认知障碍 

分 类 号：R730.55[医药卫生—肿瘤]