甘麦大枣汤对抑郁症模型大鼠前额叶和杏仁核中BDNF、SERT基因表达及血清5-HT水平的影响

Effect of Ganmai Dazao Decoction on BDNF and SERT gene expression in prefrontal lobe and amygdala and on serum level of 5-HT in rats with depression

目的研究甘麦大枣汤对抑郁症模型大鼠前额叶和杏仁核中脑源性神经营养因子(BDNF)、5-羟色胺转运体(SERT)基因表达及血清5-羟色胺(5-HT)水平的影响。方法将40只Wistar雄性大鼠随机分为正常组、模型组、甘麦大枣汤组和盐酸氟西汀组,每组10只。除正常组外,其余各组以慢性不可预见性温和刺激配合孤养的方法制备抑郁症模型。造模后,甘麦大枣汤组灌胃给予甘麦大枣汤浓缩药液(12.5 ml/kg),盐酸氟西汀组灌胃给予盐酸氟西汀药液(10 ml/kg),正常组和模型组灌胃给予蒸馏水2 ml。各组均干预28天,气相色谱-质谱联用检测血清5-HT水平,实时荧光定量PCR检测大鼠前额叶及杏仁核中BDNF mRNA、SERT mRNA的相对表达量。结果①与正常组比较,模型组大鼠血清5-HT水平降低(P<0.05),前额叶及杏仁核中BDNF mRNA、SERT mRNA相对表达量减少(P<0.05)。②与模型组比较,甘麦大枣汤组、盐酸氟西汀组大鼠血清5-HT水平升高(P<0.05);甘麦大枣汤组大鼠前额叶中BDNF mRNA相对表达量增加(P<0.05),盐酸氟西汀组大鼠前额叶中BDNF mRNA和SERT mRNA相对表达量增加(P<0.05);甘麦大枣汤组、盐酸氟西汀组大鼠杏仁核中BDNF mRNA、SERT mRNA相对表达量增加(P<0.05)。③与盐酸氟西汀组比较,甘麦大枣汤组大鼠血清5-HT水平,前额叶及杏仁核中BDNF mRNA、SERT mRNA的相对表达量差异无统计学意义(P>0.05)。结论甘麦大枣汤可能通过升高血清5-HT水平、增加前额叶和杏仁核中BDNF mRNA及杏仁核中SERT mRNA的表达,对抑郁症发挥干预作用。

Objective To study the effects of Ganmai Dazao Decoction on the expression of brain-derived neurotrophic factor(BDNF) and serotonin transporter(SERT) genes in prefrontal lobe and amygdala and on the serum level of 5-hydroxytryptamine(5-HT) in depression model rats. Methods 40 male Wistar rats were randomly assigned into normal group, model group, Ganmai Dazao Decoction group and fluoxetine hydrochloride group, 10 rats in each group. Except the normal group, the depression model was established by chronic unpredictable mild stress(CUMS) combined with orphaned method in the other groups. After modeling, Ganmai Dazao Decoction concentrate solution(12.5 ml/kg) was given to the Ganmai Dazao Decoction group, fluoxetine hydrochloride solution(10 ml/kg) was administered to the fluoxetine hydrochloride group and 2 ml of distilled water was given to the normal and model groups. All groups were treated for 28 days. The serum level of 5-HT in rats was detected by GC-MS;and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe and amygdala was determined by real-time quantitative PCR. Results ①The serum level of 5-HT and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe and amygdala decreased in the model group compared to the normal group( P<0.05).(2) Compared to the model group,the serum level of 5-HT increased in the Ganmai Dazao Decoction and fluoxetine hydrochloride groups( P<0.05);the relative expression of BDNF mRNA in prefrontal lobe increased in the Ganmai Dazao Decoction group( P<0.05) and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe increased in the fluoxetine hydrochloride group( P< 0.05);and the relative expression of BDNF mRNA and SERT mRNA in amygdala increased in the Ganmai Dazao Decoction and fluoxetine hydrochloride groups( P<0.05).(3)There were no statistically significant differences in the serum level of 5-HT and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe and amygdala between the Ganmai Dazao Decoction group and the fluoxetine hydrochloride group( P>0.05). Conclusion Ganmai Dazao Decoction may treat depression by increasing the serum level of 5-HT and the expression of BDNF mRNA in prefrontal lobe and amygdala and SERT mRNA in amygdala.