开心散联合氟西汀改善慢性压力应激小鼠抑郁样行为的效应评价研究

Evaluation of the Antidepressant Effect of Kai-Xin-San Combined with Fluoxetine on Chronic Unpredictable Mild Stress Induced Depression Model Mice

目的考察中药复方开心散联合用药氟西汀改善慢性压力应激小鼠抑郁样行为的效用与作用机制。方法采用慢性压力应激构建抑郁小鼠模型,通过糖水偏嗜实验评价开心散与氟西汀联合用药改善模型小鼠抑郁样行为的效用。采用ELISA法测定受试动物血清、海马组织和下丘脑组织中皮质醇(Cortisol)、促肾上腺皮质激素(ACTH)和促肾上腺皮质激素释放因子(CRF)的表达。采用HE染色、尼氏染色和TUNEL染色法,观察模型小鼠海马神经元损伤情况。采用Western blot法考察小鼠海马组织中Caspase-3和Caspase-9等凋亡信号通路关键蛋白的表达情况。结果开心散与氟西汀联用能显著上调模型小鼠糖水偏嗜率;同时,联合用药可抑制脑内和血清中压力应激因子的上调,减少小鼠海马区因抑郁导致的细胞凋亡,调控海马区的凋亡信号通路。结论开心散联合氟西汀可有效改善抑郁模型动物的抑郁样行为,减少氟西汀临床用量。两者联用后抑制压力应激轴激活可能是联合用药抗抑郁的作用环节。

Objective To investigate the beneficial effect of Kai-Xin-San combined with fluoxetine in improving depression-like behaviors on chronic unpredictable mild stress(CUMS)induced depression model mice.Methods The present study aimed to assess the potential of Kai-Xin-San in combination with fluoxetine to ameliorate depression-like behaviors in a CUMS induced mouse depression model.Behavioral tests,such as the sucrose preference test were employed to evaluate the efficacy of the treatment.Additionally,the levels of suppressed stress factors were measured using the ELISA method.The morphology of hippocampal tissue was evaluated using the HE staining method,Nissl Staining and TUNEL staining methods.Furthermore,western blotting analysis was utilized to determine the expression levels of proteins such as Caspase-3,and Caspase-9.Results The co-administration of Kai-Xin-San and fluoxetine resulted in a significant increase in sucrose preference rate in model mice.This effect was comparable to that of fluoxetine alone at the standard clinical dose.Furthermore,the combination treatment up-regulated the levels of suppressed stress factors,reduced the apoptosis of hippocampus induced by depression and regulated the apoptosis signaling pathway in hippocampus.Conclusion The combination of Kai-Xin-San and fluoxetine has been shown to be an effective treatment for depression-like behavior in animal models,resulting in a reduction in the required clinical dosage of fluoxetine.This effect may be attributed to the up-regulation of neurotransmitter expression,inhibition of stress axis activation,and central nervous inflammation.