Sertraline联合Aripiprazole可显著上调大鼠脑部的CREB和BDNF水平

为了探讨SSRI联合抗精神病药物对脑源性神经营养因子(brain derived neurotrophic factor, BDNF)-cAMP反应元件结合蛋白(cAMP response element binding, CREB)信号通路的影响,本研究将SD大鼠随机分成5组,每组10只,各组大鼠分别腹腔注射阿立哌唑(5 mg·kg-1·d-1,阿立哌唑组)、舍曲林(5 mg·kg-1·d-1,舍曲林组)、阿立哌唑+舍曲林(5 mg·kg-1·d-1+5 mg·kg-1·d-1,联合组),奥氮平(5 mg·kg-1·d-1,奥氮平组)和不含药物的溶液(对照组),连续注射3周。研究显示,联合组显著增加大鼠的海马区BDNF平均荧光强度和蛋白水平,但在其他组未观察到对BDNF水平的影响。另外,不同组处理对额皮质中的BDNF水平没有影响。联合组显著增加了海马和额皮质的CREB磷酸化,而单独药物处理对CREB磷酸化无影响。联合组显著增加大鼠的海马和额皮质中CREB和TrkB (BDNF受体)的mRNA表达水平,以及AKT的磷酸化。综上所述,舍曲林联合抗精神病药(阿立哌唑)可显著上调大鼠脑部的CREB和BDNF水平,并且参与调节BDNF-CREB-AKT信号通路及相关分子。

Sertraline Combined With Aripiprazole could Significantly Upregulate the Levels of CREB and BDNF in Rat Brain

In order to investigate the effect of Sertraline combined with Aripiprazole on brain derived neurotrophic factor(BDNF)-cAMP response element binding(CREB) signaling pathway. In this study, SD rats were randomly divided into 5 groups, 10 rats in each group. Each group of rats was intraperitoneally injected with aripiprazole(5 mg·kg-1·d-1, aripiprazole group), sertraline(5 mg·kg-1·d-1 sertraline group), aripiprazole+sertraline(5 mg·kg-1·d-1+ 5 mg·kg-1·d-1, combination group), olanzapine(5 mg·kg-1·d-1, olanzapine group) and drug-free solution(control group), continuous injection for 3 weeks. The results presented that the combination group significantly increased the mean fluorescence intensity and protein level of BDNF in the hippocampus of rats, but no effect on BDNF levels was observed in other groups. In addition, different groups of treatments had no effect on BDNF levels in the frontal cortex. The combination group significantly increased CREB phosphorylation in the hippocampus and frontal cortex, whereas drug treatment alone had no effect on CREB phosphorylation. The combination group significantly increased mRNA expression levels of CREB and TrkB(BDNF receptor) in the hippocampus and frontal cortex of rats, as well as phosphorylation of AKT. In conclusion, Sertraline combined with antipsychotic mecicine(aripiprazole) can significantly up-regulate CREB and BDNF levels in rat brain, and participate in the regulation of BDNF-CREB-AKT signaling pathway and related molecules.