重复经颅磁刺激对抑郁模型大鼠行为学及海马区糖皮质激素受体表达的影响☆

任慧聪谷世娜赵琳李文强张朝辉

重复经颅磁刺激对抑郁模型大鼠行为学及海马区糖皮质激素受体表达的影响☆

任慧聪*谷世娜*赵琳*李文强*张朝辉*

目的观察重复经颅磁刺激（repetitive transcranial magnetic stimulation，rTMS）对慢性应激抑郁模型大鼠的抗抑郁作用及对海马区糖皮质激素受体（glucocorticoid receptor，GR）表达的影响，探讨rTMS抗抑郁作用的可能机制。方法75只健康成年雄性大鼠随机分为造模组（60只）和空白对照组（15只），造模组采用孤养联合慢性温和不可预见应激（chronic unpredictability stimulus，CUMS）方法制备抑郁大鼠模型，为期3周，筛选造模成功的大鼠45只随机分为rTMS组、伪rTMS组和抑郁对照组，每组15只，rTMS组和伪rTMS组分别接受10 Hz 的rTMS刺激和伪刺激干预3周，抑郁对照组和空白对照组不给予干预。分别于造模前、造模后、rTMS干预后进行体重测量、蔗糖水消耗实验和强迫游泳实验评估，rTMS干预后检测大鼠海马区GR蛋白和海马GR mRNA表达水平。结果造模后，rTMS组、伪rTMS组和抑郁对照组大鼠蔗糖水消耗量较空白对照组下降，强迫游泳不动时间增加（P＜0.01）。rTMS干预后，rTMS组体重增长率、蔗糖水消耗量与伪rTMS组和抑郁对照组相比均较高（P＜0.01），强迫游泳不动时间较短（P＜0.01）。伪rTMS组及抑郁对照组海马区GR蛋白及其mRNA表达水平与rTMS组和空白对照组相比均较低（P＜0.05）。结论 rTMS能够改善CUMS抑郁模型大鼠的抑郁样行为，可能与上调海马区GR表达有关。

抑郁症 重复经颅磁刺激 大鼠 糖皮质激素受体

【Abstract】Objective To explore the effect of repetitive transcranial magnetic stimulation（rTMS）on behaviors and hippocampal glucocorticoid receptor（GR）protein expression in chronic stress depression model rats and the possible antidepressant mechanism of rTMS.Method Seventy-five male Sprague-Dawley rats were randomly divided into the blank control group（n=15）and the stress-induced group（n=60）.Singly housing and chronic unpredictable mild stress （CUMS）were used to induce the depression model in stress-induced group.Forty-five CUMS rats were selected and ran⁃domly divided into rTMS group（receiving 10 Hz rTMS intervention for 3 weeks），sham group（receiving pseudo rTMS treatments for 3 weeks）and depression group（with no further treatment）.Body weight measurements and performance in the sucrose consumption and forced swimming test（FST）were evaluated before modeling，after modeling and after inter⁃vention.The GR protein and GR mRNA expression level in the hippocampus were examined after intervention.Results Compared with control group，the body weight growth rate and the sugar water preference were significantly lower in stress-induced group（P＜0.01），and the immobility time of FST was significantly longer（P＜0.01）.After the 3-week rTMSintervention，the body weight growth rate and the sugar water preference in rTMS group，which were insignificantly differ⁃ent from control group（P＞0.05），were higher than those in sham group and depression group（P＜0.01）.The immobility times of FST in rTMS group and control group were shorter than sham group and depression group（P＜0.01）.Compared with rTMS group and control group，GR and GR mRNA expression levels in the hippocampus were significantly reduced in sham group and depression group（P＜0.01）.Conclusion rTMS can improve depression behavior of CUMS rats，which may be associated with upregulation of GR expression in the hippocampus.

【Key Words】Depression Repetitive transcranial magnetic stimulation Rats Glucocorticoid receptor

近年来，大量研究表明抑郁症患者大脑诸多区域糖皮质激素受体（glucocorticoid receptor，GR）表达有所减少［1］，在与情绪、认知及应激调节等均有重要关系的海马组织中，角回3（cornu ammonis 3，CA3）区、齿状回（fascia dentate，DG）区等均呈现GR表达减少［2-3］。……