五味子乙素对慢性应激抑郁大鼠海马BDNF/TrkB/CREB通路的影响

目的 研究五味子乙素对慢性应激抑郁大鼠海马脑源性神经营养因子（BDNF）/酪氨酸激酶B（TrkB）/环磷腺苷效应元件结合蛋白（CREB）信号通路的影响。方法 40只SD大鼠随机选择10只作为对照组，其余大鼠采用慢性不可预知温和应激（chronic unpredictable mild stress，CUMS）结合孤养制备抑郁症模型，造模结束后随机分为3组：模型组、盐酸氟西汀（3 mg·kg^-1）组、五味子乙素（5 mg·kg^-1）组，每天ig给药1次，连续8周。分别于造模前、造模后及给药后进行旷场、悬尾、强迫游泳行为学实验；通过苏木素-伊红（HE）染色观察大鼠海马形态学改变；免疫组织化学染色（IHC）法观察大鼠海马BDNF蛋白表达；实时荧光定量PCR（qRT-PCR）法检测大鼠海马BDNF、TrkB、CREB mRNA相对表达量；Westernblotting检测大鼠海马BDNF、TrkB、CREB蛋白相对表达量。结果 与对照组比较，模型组大鼠旷场实验水平、垂直得分显著降低（P＜0.05），悬尾不动时间和强迫游泳漂浮时间显著增加（P＜0.05）；HE染色结果显示海马神经元结构损伤，IHC结果显示海马BDNF表达明显降低；海马BDNF、TrkB、CREB mRNA及蛋白相对表达显著降低（P＜0.05）。与模型组比较，盐酸氟西汀及五味子乙素组大鼠水平、垂直得分显著增加（P＜0.05），不动时间和漂浮时间显著减少（P＜0.05）；海马神经元结构明显复原，海马组织中BDNF染色明显增加；BDNF、TrkB、CREB mRNA和蛋白相对表达量显著增加（P＜0.05）。结论 五味子乙素可以改善慢性应激抑郁大鼠抑郁样行为、海马区神经元数量及形态，其机制可能与上调BDNF/TrkB/CREB信号通路有关。

Effects of schisandrin B on hippocampal BDNF/TrkB/CREB pathway in rats with chronic stress depression

Objective To study the effect of schizandrin B on the hippocampal brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB)/cyclic adenosine phosphate response element binding protein (CREB) signaling pathway in rats with chronic stress depression. Method Among 40 SD rats, 10 were selected as control group, and the remaining 30 rats were randomly divided into three groups after establishing the chronic stress depression rat model, namely the model group and the fluoxetine hydrochloride group (3 g·kg^-1). schisandrin B group (5 g·kg^-1). The rats were given by ig administration for eight weeks, once a day. Behavioral experiments were performed to evaluate the depression state of the rats before modeling, after modeling and after the injection. The hematoxylin-eosin staining (HE) was used to observe the morphological changes in hippocampus of rats. The immunohistochemical staining (IHC) was used to quantitatively detect BDNF protein expression in rat hippocampus; the real-time fluorescent quantitative PCR (qRT-PCR) method was used to quantitatively detect the relative expression of BDNF, TrkB, CREB mRNA in rat hippocampus, and Western blotting was used to quantitatively detect the relative expression of BDNF, TrkB, and CREB protein in rat hippocampus. Results Compared with control group, the horizontal and vertical scores, immobility time and floating time were significantly increased in model group (P<0.05). HE staining results showed that hippocampal neuron structure was damaged. Immunohistochemical staining showed that the expression of BDNF was significantly decreased (P<0.05), and the mRNA and protein expressions of BDNF, TrkB and CREB were significantly decreased (P<0.05). Compared with model group, the horizontal and vertical scores were significantly increased and the immobility time and floating time were significantly decreased in fluoxetine hydrochloride group and schisandrin B group (P<0.05), and the hippocampal neuron structure was significantly recovered. Immunohistochemical staining showed that the expression of BDNF was significantly increased (P<0.05), and the mRNA and protein expressions of BDNF, TrkB and CREB were significantly increased (P<0.05). Conclusion Schisandrin B can significantly improve the depression-like behavior of rats after chronic stress stimulation and enhance the regeneration and repair of neurons in the hippocampus, and the mechanism may be related to the up-regulation of the BDNF/TrkB/CREB signaling pathway in the hippocampus of rats.