二十二碳六烯酸抗抑郁作用及其对海马神经元caspase-3表达的影响

The anti-depression effects of docosahexaenoic acid and its effects on the expression of caspase-3 in hippocampal neuron

目的 观察二十二碳六烯酸（docosahexaenoic acid,DHA）对抑郁症的治疗作用及其对海马神经元caspase-3表达的影响.方法 50只SD大鼠随机分为5组（空白对照组,抑郁模型组,氟西汀组,DHA组,氟西汀与DHA联合用药组）,每组10只,连续21 d每天给予不同刺激,建立慢性应激不可预见抑郁大鼠模型.21 d后强迫游泳实验进行行为学检测,HE染色检测海马CA1、CA2、CA3区锥体细胞的形态学变化.荧光实时定量PCR和Western Blot检测海马神经元caspase-3的变化.结果 行为学检测显示,抑郁模型组、DHA组、DHA联合氟西汀组大鼠在水中的游泳不动时间分别为（113.33±9.50）s、（81.67±7.68）s和（73.00±8.54）s.与抑郁模型组相比,DHA组和DHA联合氟西汀组大鼠在水中游泳不动时间减少（t=8.164,9.855,P＜0.01）.HE染色切片可见DHA使大鼠海马CA1、CA2、CA3区神经元数量部分恢复,排列致密,可减少海马神经元凋亡.qPCR和WB结果显示DHA单独或联合氟西汀可抑制海马神经元caspase-3 mRNA和蛋白的表达.结论 DHA对慢性应激不可预见抑郁模型大鼠有治疗及辅助治疗作用,其机制与DHA减少海马神经元凋亡、下调caspase-3有关.

Objective To explore the therapeutic effects of docosahexaenoic acid （DHA） on depression,and its influence on the expression of caspase-3 in hippocampal neuron.Methods A total of 50 SD rats were randomly divided into 5 groups （control,model,fluoxetine,DHA,combination group）,10 rats in each group.SD rats were given different stimuli for 21 days to set up unforeseeable chronic stress depression model.After 21 days,the changes of behaviors in forced swimming test and morphology change in CA1,CA2 and CA3 in hippocampal neurons were observed.The change of caspase-3 in hippocampal neuron were detected by real-time PCR and western blot.Results Behavioral results showed that the swimming immobility time in depression model group,DHA group and combination group were respectively（113.33±9.50） s,（81.67±7.68） s and（73.00±8.54） s.Compared with depression model group,the DHA group and DHA combined with fluoxetine group obviously reduced the swimming immobility time of rats（t=8.164,9.855,P＜0.01）.HE stain result showed DHA could partly recovered the number of hippocampal neurons in CA1,CA2 and CA3 and reduced apoptosis.qPCR and WB results showed DHA alone or DHA combined with fluoxetine could inhibit mRNA and protein level of caspase-3 in hippocampal neurons.Conclusion DHA can improve depression to a certain extent in a rat model of unforeseeable chronic stress depression,which might work through inhibition of neuron apoptosis and caspase-3 expression in hippocampal neurons.