焦虑性抑郁模型大鼠脑区单胺递质含量与神经因子表达的变化

Changes of content of monoamine neurotransmitters and expression of neurotrophic factors in brain regions of rat models of anxious depression

目的研究焦虑性抑郁模型大鼠海马、杏仁核、前额叶皮质内单胺递质的含量变化及脑内神经营养因子的表达趋势,探讨其可能的发病机制。方法 60只SD大鼠随机分为正常对照组、溶媒对照组、焦虑模型组、抑郁模型组、焦虑性抑郁模型组,每组12只。采用慢性束缚应激联合皮质酮注射的方法建立焦虑性抑郁大鼠模型,造模时间为21 d,造模结束后采用高架十字迷宫测试,旷场实验,强迫游泳实验评价大鼠的焦虑和抑郁样行为,HPLC-ECD法检测大鼠海马、杏仁核、前额叶皮质的单胺递质5-HT、NE、DA含量,蛋白印迹法检测大鼠各脑区神经营养因子BDNF、NT-3的含量。结果焦虑性抑郁模型组大鼠在进入开臂的时间、次数、旷场中自主活动次数均与焦虑组相当,与对照组及抑郁组比较差异有显著性(P<0.01或P<0.05),在强迫游泳中的不动时间显著增加,与对照组及焦虑组对比差异有显著性(P<0.01);同时,与对照组比较,焦虑性抑郁模型组大鼠海马5-HT、杏仁核及前额叶皮质区的5-HT和NE含量均显著下降(P<0.01或P<0.05);此外,与对照组比较,焦虑性抑郁模型组大鼠各脑区BDNF、NT-3含量显著下降(P<0.01或P<0.05),同时与焦虑组比较,BDNF含量显著下降(P<0.05)。结论焦虑性抑郁模型组大鼠具有显著的焦虑及抑郁样行为,其发病机制可能与脑内海马、杏仁核、前额叶皮质区域的单胺递质含量降低及神经营养因子BDNF、NT-3表达下调有关。

Objective To study the content of monoamine neurotransmitters and neurotrophic factor in the hippocampus,amygdala and prefrontal cortex in anxious depression rats,and explore the possible pathogenesis. Methods 60 SD rats were randomly divided into normal group,vehicle group,anxiety group,depression group,and anxious depression group,12 rats in each group. Chronic restraint stress combined with corticosterone injection was used to establish anxiety and depression model,the modeling time was 21 d. After modeling,elevated plus maze test,open field test,and forcedswimming test were used to evaluate the anxiety and depression-like behavior,HPLC-ECD was used to detect the content of 5-HT,NE,and DA in the hippocampus,amygdala,and prefrontal cortex of rats. Western-blotting was used to detect the expression of BDNF and NT-3 in rats. Results Rats in anxious depression model group were comparable to the anxiety group in time and frequency entering open arm time,and number of locomotor activity in open field,and it had a significant difference when compared with the control and depression groups（ P〈0. 01 or P〈0. 05）. Immobile time in anxious depression model rats was increased significantly when compared with the control and anxiety groups（ P〈0. 01）. Meanwhile,compared with the control group,5-HT in hippocampus and 5-HT,NE in amygdala or prefrontal cortex were significantly decreased in the depressive rats with anxiety（ P〈0. 01 or P〈0. 05）. Moreover,the content of BDNF and NT-3 was significantly decreased in each brain regions compared with the control group（ P〈0. 01 or P〈0. 05）,and BDNF levels were obviously decreased compared with the anxiety group（ P〈0. 05）. Conclusions Rats of anxious depression have significant anxiety and depression-like behaviors. Its mechanism may be associated with the down-regulation of monoamine neurotransmitters and neurotrophic factors BDNF and NT-3 in hippocampus,amygdala,and prefrontal cortex region.