鸡豆黄素A对围绝经期抑郁症大鼠的神经保护作用及机制研究

Research on effects and mechanism of Bioch A neuroprotection to rats in perimenopausal depression disorder

目的探讨鸡豆黄素A(Bioch A)对围绝经期抑郁症(PDD)模型大鼠行为学影响及神经保护机制。方法采用大鼠双侧卵巢摘除(OVX)与慢性不可预知性温和应激(CUMS)两步法制备PDD动物模型。采用旷场实验、强迫游泳实验观察大鼠行为学变化;高效液相色谱-电化学检测法测定大鼠海马组织多巴胺(DA)、去甲肾上腺素(NA)及五羟色胺(5-HT)的含量; Western blot检测海马白细胞介素-1β(IL-1β)、半胱氨酸天门冬氨酸蛋白水解酶-1(Caspase-1)、蛋白激酶A(PKA)、磷酸化蛋白激酶A(p-PKA)、cAMP反应元件结合蛋白(CREB)、磷酸化cAMP反应元件结合蛋白(pCREB)、脑源性神经营养因子(BDNF)、酪氨酸蛋白激酶B(TrkB)的表达。结果与模型组相比,给予Bioch A和氟西汀治疗后,抑郁症大鼠水平和竖直运动得分均明显增加,强迫游泳不动时间显著降低(P <0. 05,P <0. 01),海马IL-1β、Caspase-1表达水平均不同程度降低(P <0. 05,P <0. 01),5-HT的含量明显升高,PKA及CREB磷酸化水平及BDNF、TrkB mRNA表达水平均不同程度升高(P <0. 05,P <0. 01)。结论 Bioch A对PDD有一定的对抗作用,其机制主要与增加海马5-HT含量及上调海马cAMP-CREB-BDNF信号通路蛋白表达有关。

Objective To explore behavioral influence and neuroprotective mechanism of Bioch A in inperimenopausal depression disorder( PDD) rats model. Methods Rats model of PDD was established via two-step methods ovariectomy( OVX) and chronic unpre-dictable mild stress( CUMS). Rats ’ behavioral changes were observed through open-field tests and forced-swimming tests;a HPLC method with electrochemical detector is applied for determination of dopamine( DA),arterenol( NA) and 5-hydroxytryptamine( 5-HT) content in rats;Western blot was used to detecting expression of interleukin-1β( IL-1β),interleukin-1 converting enzyme( Caspase-1),protein kinase A( PKA),phosphorylation protein kinase A( p-PKA),cAMP response element binding pro-tein( CREB),phosphorylation cAMP response element binding pro-tein( p-CREB),brain-derived neurotrophic factor( BDNF),and tyrosine protein kinase B( TrkB). Results After Bioch A and fluoxetine treatment,rats in PDD scored obviously higher at both horizontal motion and vertical motion;immobility time in forced swimming was significantly shortened( P < 0. 05,P < 0. 01);expression level of IL-1β and Caspase-1 lowered in different degrees( P < 0. 05,P < 0. 01);5-HT content was clearly increased;phosphorylation level of PKA and CREB,expression level of BDNF,TrkB and mRNA all rose in different degrees( P < 0. 05,P < 0. 01),in comparison with those of model group.Conclusion Bioch A has a certain antagonistic effect on PDD,and its mechanism is mainly related to increasing hippocampal 5-HT content and up-regulating hippocampal cAMP-CREB-BDNF signaling pathway protein expression.