目的 探讨曲古抑菌素A对慢性不可预见性应激(CUMS)模型大鼠抑郁样行为及脑源性神经营养因子(BDNF)表达的调节作用.方法 将40只成年雄性SD大鼠随机分为正常对照组、模型组、氟西汀组和曲古抑菌素A组.采用不同应激因子交替刺激加孤养复制CUMS模型;采用体重增长率、糖水偏嗜试验和旷场试验评估大鼠的行为学变化;采用Western blot测定大鼠海马组织中BDNF和磷酸化环磷腺苷反应元件结合蛋白(p-CREB)的表达水平.结果 造模21 d后,模型组大鼠体重增长率、糖水偏嗜度、水平和垂直运动评分较正常对照组显著降低(P＜0.05);氟西汀组和曲古抑菌素A组大鼠体重增长率、糖水偏嗜度、垂直和水平运动评分均较模型组显著增加(P＜0.05).Western blot结果显示,模型组大鼠海马区BDNF和p-CREB表达水平显著低于正常对照组(P＜0.05),而氟西汀组和曲古抑菌素A组大鼠海马区BDNF和p-CREB表达水平显著高于模型组(P＜0.05).结论 曲古抑菌素A可有效改善抑郁模型大鼠的抑郁样行为,其抗抑郁作用可能与调节CREB-BDNF通路促进BDNF表达有关.%Objective To investigate the effects of Trichostatin A on behaviors and expression of brain-derived neu-rotrophic factor (BDNF) in model rats with chronic unpredictable mild stress-induced depression (CUMS).MethodsForty adult male SD rats were randomly divided into normal control group,model group,Fluoxetine group and Tricho-statin A group.The model of depression was established with alternative unpredictable stress combining isolated livingconditions.The rat ethological changes were assessed by body weight,sucrose consumption and open field test.Theprotein expressions of BDNF and phosphorylated cAMP responsive element binding protein (p-CREB) were measured byWestern blot.Results After modeling for 21 days,the body weight,sucrose consumption,horizontal motion and verticalmotion scores in model group were significantly lower than those of normal control group (P ＜ 0.05);however,these etho-logical indexes in Fluoxetine group and Trichostatin A group were obviously increased compared with those of modelgroup (P ＜ 0.05).The results of Western blot showed that the expression of BDNF and p-CREB in model group were significantly lower than those of normal control group (P ＜ 0.05),while the expression of BDNF and p-CREB in Fluoxetinegroup and Trichostatin A group were significantly higher than those of model group (P ＜ 0.05).Conclusion TrichostatinA can effectively improve depression-like behaviors in CUMS model rats,its anti-depressive effect may be attributedto up-regulation of the CREB-BDNF signaling pathway.
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