目的：探讨SD大鼠WBI后海马区NFATc 4／3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、NFATc 4／3、p⁃NFATc 4／3、GSK⁃3β表达量变化。结果照射后6、12 hNFATc 4／3、p⁃NFATc 4／3表达无变化，照射后1 d随照射剂量增加p⁃NFATc 4／3表达水平与0 Gy相比明显升高（2 Gy P＝0.014、10 Gy P＝0.011、20 Gy P＝0.000），而NFATc 4／3的表达水平无变化；照射后3 d、1周和2周NFATc 4／3表达水平与0 Gy相比显著下降（3 d 2 Gy P＝0.040、10 Gy P＝0.000、20 Gy P＝0.000、1周2 Gy P＝0.692、10 Gy P＝0.032、20 Gy P＝0.021、2周2 Gy P＝0.001、10 Gy P＝0.000、20 Gy P＝0.000），而p⁃NFATc 4／3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NFATc 4／3信号通路有抑制作用，推测放射性认知功能障碍可能与NFATc 4／3信号通路相关。%Objective This study is to investigate the changes in the NFATc 4/3 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, NFATc 4/3, p⁃NFATc 4/3, and GSK⁃3β. Results There were no significant changes in the expression of NFATc 4/3 or p⁃NFATc 4/3 at 6 and 12 hours after whole brain radiation. At 1 day after radiation,compared with the control group,the expression of p⁃NFATc 4/3 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 NFATc 4/3 between the radiation group and the control group. The expression of NFATc 4/3 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⁃NFATc 4/3 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 NFATc 4/3 signaling pathway in rat hippocampus. Combined with our previous results,this study suggests that radiation⁃induced cognitive dysfunction is associated with the NFATc 4/3 signaling pathway.
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