卵巢切除联合束缚应激对小鼠抑郁样行为及海马齿状回神经前体细胞的影响

Effect of ovariectomy combined bondage stress on depression-like behavior and the hippocampal dentate gyrus progenitors in mice

目的 探讨卵巢切除联合束缚应激对小鼠抑郁样行为的诱导是否有协同作用,小鼠抑郁样行为是否伴随海马齿状回颗粒下区（SGZ）神经前体细胞状态的变化.方法 C57B/L小鼠40只,随机分为4组,单纯卵巢切除组,单纯束缚应激组,卵巢切除联合束缚应激组,假手术组.束缚应激21 d后,通过旷场实验、蔗糖偏好实验、强迫游泳实验检测小鼠抑郁样行为反应.免疫组织化学方法检测海马SGZ区Ki67及DCX表达,并做细胞计数.结果 卵巢切除联合束缚应激21d后体质量为（18.70±0.25）g,和假手术组[（20.96±0.24）g]比较差异有统计学意义.卵巢切除联合束缚应激21 d后,强迫游泳时间延长至（165.60±9.60）s,和假手术组[（140.28± 12.30）s]比较差异具有统计学意义（P＜0.05）,同时可见探索行为减少,蔗糖偏好率下降,单独卵巢切除或束缚应激对小鼠抑郁样行为影响相对较小.卵巢切除联合束缚应激导致小鼠SGZ区Ki67阳性细胞数为8.6± 2.4/section,DCX阳性细胞数为4.2±1.4/section,和假手术组[Ki67为（16.7±2.5/section）；DCX为（12.6±2.3/section）]比较,明显减少（P＜0.05）.结论 雌激素水平低下联合束缚应激对抑郁发病有协同作用,并抑制海马SGZ区神经前体细胞功能状态.

Objective To explore whether synergistic action occurs in development of depression-like behaviors using ovariectomy combined bondage stress,and whether hippocampal neural progenitor state is changed following depression-like behaviors in mice.Methods Forty female C57B/L mice were divided into four groups randomly,which included ovariectomy,bondage stress,ovariectomy combined bondage stress and sham groups.Depression-like behaviors were evaluated by open field test,sucrose preference and forced swimming test after animals had been treated for 21 days.All animals were fixed by 4％ PA perfusion through left ventricle,then brain was removed,and coronal serials sections were made.Expression of Ki67 and DCX was tested by immunohistochemistry or immunofluorescence in subgranular zone of hippocampal dentate gyrus （SGZ）.Results Body weight（（18.70± 0.25） g vs （20.96±0.24）g）,novelty-seeking behavior and sucrose preference decreased in ovariectomy combined bondage stress-group compared with those in sham group （P＜0.05）,but forced swimming time increased in shame group（（165.6±9.6）s vs （140.28±12.3） s）.Likewisely,Ki67-positive cells（（8.6±2.4）/section） and DCX-positive cells（（4.2±1.4）/section） in SGZ decreased in ovariectomy combined bondage stress-group compared with those in sham group（Ki67：（16.7±2.5/section）,DCX：（12.6±2.3/section） （P＜0.05）.Unsimilarly,depressionlike behaviors had little change in ovariectomy-or bondage stress-groups compared with those in sham-group.Conclusion Ovariectomy combined bondage stress has synergistic action in development of depression,and inhibits the active state of progenitor in SGZ in mice.