氯丙咪嗪联合睡眠剥夺对抑郁模型大鼠行为及海马CA3区神经元凋亡的影响

Effect of clomipramine combine sleep deprivation on depression rat behavior and hippocampal CA3 neuron apoptosis

目的 研究氯丙咪嗪联合睡眠剥夺对抑郁模型大鼠行为及海马CA3区神经元凋亡的影响.方法 慢性温和不可预知性刺激法制备50只抑郁症模型大鼠,将其随机分为抑郁组、氯丙咪嗪组（5mg/kg灌胃）、睡眠剥夺组（连续36 h全睡眠剥夺）、氯丙咪嗪联合睡眠剥夺组,对照组,每组各10只.各组干预28 d后利用旷场试验、水迷宫实验检测大鼠行为改变.RT-PCR、Western blot检测各组海马CA3区神经元GDNF及Bcl-2表达.TUNEL法检测各组海马CA3区神经元凋亡比率.结果 氯丙咪嗪联合睡眠剥夺组进行药物及睡眠剥夺干预28 d后旷场试验水平评分、垂直运动评分与潜伏期分别为（75.6±7.3）分、（26.4±4.3）分、（1.1±0.2）s,与对照组（79.4±6.8）分、（28.6±5.7）分、（1.0±0.4）s比较,均差异无统计学意义（P＞0.05）;与其他三组比较,水平运动评分和垂直运动评分升高（P＜0.05）,潜伏期降低（P＜0.05）.水迷宫实验显示联合组逃逸潜伏时间也呈逐渐缩短趋势.对照组和联合组的GDNF、Bcl-2表达显著高于其余3组（P＜0.05）,而这两组之间差异无统计学意义（P＞0.05）.睡眠剥夺组凋亡比率最高,为（55±6）％,显著高于对照组和联合组的（14±3）％和（19±4）％.结论 氯丙咪嗪联合睡眠剥夺能够有效改善抑郁模型大鼠的行为能力和抑制海马CA3区神经元凋亡,其作用可能与提高海马CA3区GDNF、Bcl-2有关.

Objective To analyze the effect of clomipramine combine sleep deprivation on depression rat behavior and hippocampal CA3 neuron apoptosis.Methods Chronic unpredictable mild stimulation was used to establish 40 depression model rats.They were randomly divided into depression group,clomipramine group （5 mg/kg orally）,sleep deprivation group （36 h continuous full sleep deprivation）,chlorpromazine combination of sleep deprivation group,and then selected 10 rats as control group.Open-field test and water maze test were used to test rats＇ behavioral change after 28 days intervention.RT-PCR,Western blot were used to detect the GDNF and Bcl-2 expression of hippocampal CA3 neurons.TUNEL assay was performed to test hippocampal CA3 neuron apoptosis ratios in each group.Results Open-field test level score,vertical score and latency of combination group were （75.6±7.3）,（26.4±4.3）,（1.1±0.2）,and showed no significant difference with those of control group（（79.4 ±6.8）,（28.6±5.7）,（1.0±0.4）） after 28 d intervention （P〉0.05）,while the level score,vertical score were significantly higher than those in other three groups（P〈0.05）,and the latency period was significantly lower than that in other three groups （P〈0.05）.The combined group showed a trend of gradually shortened in water maze escape latency.GDNF,Bcl-2 expression of control group and combined group was significantly higher than those in other three groups （P〈0.05）,while the difference between the two groups was not statistically significant （P〉0.05）.Sleep deprivation group＆#39; apoptotic rate was the highest （55±6）%,significantly higher than the control group and the combination group （（14±3） % and （19±4）%）.Conclusion Clomipramine combined sleep deprivation can improve the ability of rat model of depression and suppression of acts of hippocampal CA3 neuron apoptosis,and its effect may be related to increased hippocampal CA3 GDNF,Bcl-2 level.