目的 研究五味子乙素對慢性應(yīng)激抑郁大鼠海馬腦源性神經(jīng)營養(yǎng)因子（BDNF）/酪氨酸激酶B（TrkB）/環(huán)磷腺苷效應(yīng)元件結(jié)合蛋白（CREB）信號通路的影響。方法 40只SD大鼠隨機(jī)選擇10只作為對照組，其余大鼠采用慢性不可預(yù)知溫和應(yīng)激（chronic unpredictable mild stress，CUMS）結(jié)合孤養(yǎng)制備抑郁癥模型，造模結(jié)束后隨機(jī)分為3組：模型組、鹽酸氟西?。? mg·kg^-1）組、五味子乙素（5 mg·kg^-1）組，每天ig給藥1次，連續(xù)8周。分別于造模前、造模后及給藥后進(jìn)行曠場、懸尾、強(qiáng)迫游泳行為學(xué)實驗；通過蘇木素-伊紅（HE）染色觀察大鼠海馬形態(tài)學(xué)改變；免疫組織化學(xué)染色（IHC）法觀察大鼠海馬BDNF蛋白表達(dá)；實時熒光定量PCR（qRT-PCR）法檢測大鼠海馬BDNF、TrkB、CREB mRNA相對表達(dá)量；Westernblotting檢測大鼠海馬BDNF、TrkB、CREB蛋白相對表達(dá)量。結(jié)果 與對照組比較，模型組大鼠曠場實驗水平、垂直得分顯著降低（P＜0.05），懸尾不動時間和強(qiáng)迫游泳漂浮時間顯著增加（P＜0.05）；HE染色結(jié)果顯示海馬神經(jīng)元結(jié)構(gòu)損傷，IHC結(jié)果顯示海馬BDNF表達(dá)明顯降低；海馬BDNF、TrkB、CREB mRNA及蛋白相對表達(dá)顯著降低（P＜0.05）。與模型組比較，鹽酸氟西汀及五味子乙素組大鼠水平、垂直得分顯著增加（P＜0.05），不動時間和漂浮時間顯著減少（P＜0.05）；海馬神經(jīng)元結(jié)構(gòu)明顯復(fù)原，海馬組織中BDNF染色明顯增加；BDNF、TrkB、CREB mRNA和蛋白相對表達(dá)量顯著增加（P＜0.05）。結(jié)論 五味子乙素可以改善慢性應(yīng)激抑郁大鼠抑郁樣行為、海馬區(qū)神經(jīng)元數(shù)量及形態(tài)，其機(jī)制可能與上調(diào)BDNF/TrkB/CREB信號通路有關(guān)。

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.

R285.5

黑龍江省應(yīng)用技術(shù)研究與開發(fā)計劃項目(GA19C108)