目的 观察不同刺激参数重复经颅磁刺激(rTMS)对慢性不可预见应激(CUS)模型大鼠行为学的作用,并观察其对大鼠脑源性神经营养因子(BDNF)水平的影响.方法 64只SD大鼠随机分为对照组(8只)、模型组(8只)和干预组(共6个亚组,每组8只).对照组正常饲养21d后连续7d给予rTMS假刺激;模型组在造模后连续7d给予rTMS假刺激;干预组在造模后每天给予不同频率和强度的rTMS刺激,连续7d.实验期间观察大鼠体质量的变化,并采用运动箱和强迫游泳实验评估大鼠抑郁样行为,最后以酶联免疫吸附法测定大脑BDNF的水平.结果 (1)造模结束后,对照组大鼠的体质量、强迫游泳静止时间与其他两组相比均存在显著性差异(P<0.01,P<0.05),而模型组和干预组大鼠比较没有上述差异(P> 0.05).各组大鼠水平运动距离没有显著性差异(P>0.05).(2)rTMS干预后,①模型组大鼠的体质量显著低于对照组及干预组(5 Hz,0.84/1.26 T和10 Hz,0.84/1.26 T) (P <0.05).②各组大鼠水平运动距离之间没有显著性差异;模型组强迫游泳静止时间百分比明显高于对照组及干预组(P<0.05).③模型组BDNF的水平低于对照组,而一定刺激条件的rTMS可以改善这一现象.④双因素方差分析显示,刺激频率可能是改善大鼠抑郁行为和调节BDNF的关键因素,而且5 Hz的抗抑郁效应更为显著.结论 不同刺激参数的rTMS对CUS动物抑郁行为的改善作用存在差异,大脑BDNF水平的变化可能参与了这一改善过程.
Objective To investigate the effect of different parameters of rTMS on the behavior and the levels of cerebral BDNF of chronic unpredictable stress (CUS) model rats.Method 64 adult male Sprague Dawley rats were randomly divided into sham group (8 rats),model group (8 rats),treatment group (48 rats averaged into 6 subgroups with different rTMS parameters).Rats in sham group were treated with fake rTMS for consecutive 7 days after 21-day normal breeding,rats in model group were treated with fake rTMS for consecutive 7 days after successful modeling,and rats in treatment group were treated with rTMS with different parameters according with their subgroup for consecutive 7 days after successful modeling.The body weight of all rats were recorded weekly.The open field test and forced swimming test were used to evaluate the depression-like behavior.Level of cerebral BDNF was measured by Elisa assay at the end of the study.Results (1) After successful modeling,there were significant differences in body weight and immobility time of forced swimming among sham group,model group and treatment group (P < 0.01 or 0.05).While no significant difference was found between model group and treatment group in body weight and immobility time (P > 0.05).There was no significant difference in distance of horizontal movement among the three groups (P > 0.05).(2) After the 7-day rTMS or fake rTMS,average body weight in model group was significantly lower than that in sham group and in high-frequency treatment group with the parameter of 5 Hz,0.84/1.26 Tesla or 10 Hz,0.84/1.26 Tesla (P < 0.05).There was no significant difference in distance of horizontal movement among the three goups,while the immobility time of forced swimming was significantly longer in model group than that in sham group and high-frequency treatment group (P <0.05).Level of cerebral BDNF in model group was significantly lower than that in sham group,which could be alleviated by rTMS at some parameters.Two-way ANOVA