大鼠WBI后海马区NFATc4/3信号通路相关因子改变的研究

doi:10.3760/cma.j.issn.1004-4221.2017.01.018

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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。

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	陈清清
	周梦耘
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	张奇贤
	曹毅
	田野

关键词 ：全脑照射, NFATc4/3基因, 认知障碍

Abstract：

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.

Key words： Whole-brain irradiation NFATc4/3 gene Cognitive dysfunction

收稿日期: 2015-10-22

基金资助:

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)

通讯作者: 田野,Email:dryetian@126.com

引用本文:

陈清清,周梦耘,孙锐等. 大鼠WBI后海马区NFATc4/3信号通路相关因子改变的研究[J]. 中华放射肿瘤学杂志, 2017, 26(1): 79-83.

Chen Qingqing,Zhou Mengyun,Sun Rui et al. The change of NFATc4/3 signaling pathway in the rat hippocampus following whole brain irradiation[J]. Chinese Journal of Radiation Oncology, 2017, 26(1): 79-83.

链接本文:

http://journal12.magtechjournal.com/Jweb_fszlx/CN/10.3760/cma.j.issn.1004-4221.2017.01.018 或 http://journal12.magtechjournal.com/Jweb_fszlx/CN/Y2017/V26/I1/79

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