35GHz毫米波急性辐照小鼠诱发丘脑-垂体-肾上腺皮质轴功能改变和Th1／Th2失衡

Functional changes of HPA axis and Th1/Th2 imbalance in mice acutely exposed to 35 GHz millimeter-wave

目的观察35GHz毫米波诱发的急性应激反应中重要细胞因子及下丘脑-垂体-肾上腺皮质（HPA）轴相关激素的表达规律，旨在探索神经-内分泌-免疫系统之间内在的关联。方法以420mW／cm2功率密度的35GHz毫米波源急性辐照BALB／c小鼠60s。于照后不同时间，用ELISA方法检测血清中IFN-γ、IL-4等细胞因子的表达水平，并用RT—PCR和免疫组织化学方法检测下丘脑促肾上腺皮质素释放激素（CRH）和海马区糖皮质激素受体（GR）的变化。结果Th1和Th2型细胞因子IFN-γ和IL-4在照后3d均升高至峰值（t=-6．59、-2．28，P〈0．05），至照后7d仍明显高于对照组；其比值在照后1和3d明显增高，即发生了明显的Th1／Th2平衡向Th1免疫反应漂移的现象。毫米波急性辐照后下丘脑CRHmRNA含量出现持续性升高，至7d升高至峰值（t=-7．03，P〈0．05）；而海马GRmRNA含量在3d达到峰值后迅速降低至对照组水平。下丘脑CRH和海马GR蛋白表达的趋势与其mRNA水平变化基本一致。结论小鼠经35GHz毫米波急性辐照后，Th1／Th2平衡向Th1方向偏移；同时应激增加的下丘脑CRH和海马GR对IFN-γ等因子的反馈抑制，使向Th1偏移的免疫失衡现象得以改善，可缓解过度应激造成的免疫损伤。

Objective To investigate the expression pattern of cytokines and HPA axis hormones in acute stress reaction induced by 35 GHz millimeter-wave （MMW） radiation, and to explore the intrinsic association among the nerve-endocrine-immune system. Methods BALB/c mice were exposed to 35 GHz MMW with an average power density of 420 mW/cm2 for 60 s. The contents of IFN-γ and IL-4 in serum were measured and the expression level of hypothalamic corticotropin releasing hormone （CRH） and hippocampus glucocorticoid receptor （GR） in brain were analyzed at different time points after MMW exposure. Results The levels of IFN-γ and IL-4 and the cytokines of Th1 and Th2 increased to peak levels （ t = - 6. 59, - 2.28, P 〈 0. 05 ） at 3 d after exposure, and were still high up to 7 d after exposure. The ratio of Th1/Th2 （IFN-γ IL-4） increased significantly at 1 d and 3 d post-exposure, which suggested that Th1/Th2 balance drifted to Th1 immune response. After acute MMW exposure, the level of hypothalamic CRH mRNA increased gradually and approached to a peak value at 7 d （t = - 7.03, P 〈 0.05）. The expression level of hippocampal GR mRNA reached the peak at 3 d and then declined to control level. Meanwhile, the changes of hypothalamic CRH and hippocampal GR were consistent with the changes of their mRNA expressions. Conclusions Th1/Th2 balance in mice shifts toward Th1 after 35 GHz MMW acute exposure and the imbalance of Th1 shift can be improved obviously due to the feedback inhibition of IFN-γ and other eytokines by increased hyputhalamic CRH and hippocampal GR induced bystress, which can alleviate the immune damage caused by excessive stress.