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-1βand 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 BD-NF, Trk B 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.%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)、c AMP反应元件结合蛋白(CREB)、磷酸化c AMP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(Trk B)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、Trk B 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c AMP-CREB-BDNF信号通路蛋白表达有关.
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