毛蕊花糖苷通过调控BDNF-TrkB信号通路改善CUMS大鼠的抑郁样行为

目的:观察毛蕊花糖苷(acteoside)对慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)大鼠抑郁样行为的影响,并探讨脑源性神经营养因子-原肌球蛋白受体激酶B(brain-derived neurotrophic factor-tropomyosin receptor kinase B,BDNF-TrkB)信号通路在其中的作用机制。方法:采用CUMS结合孤养的方式制备抑郁模型大鼠,成模后随机分为模型组、盐酸氟西汀(20 mg/kg)组和毛蕊花糖苷(30 mg/kg、60 mg/kg和120 mg/kg)组,每组18只,另取18只正常大鼠作为对照组,连续灌胃给药3周。采用强迫游泳实验和糖水偏好实验检测大鼠抑郁样行为的变化;免疫荧光和Western blot法检测大鼠海马BDNF-TrkB信号通路相关蛋白的表达情况;ELISA法检测脑组织中单胺类神经递质5-羟色胺(5-HT)、多巴胺(DA)和去甲肾上腺素(NE)的含量。结果:与对照组比较,模型组大鼠强迫游泳不动时间明显延长,糖水偏好量明显下降,海马BDNF和TrkB的表达均明显降低,脑组织中5-HT、DA和NE含量均显著减少;与模型组比较,盐酸氟西汀组和毛蕊花糖苷各剂量组以上各检测指标均得到显著逆转(P0.05)。结论:毛蕊花糖苷可能通过上调海马BDNF-TrkB信号通路、增加脑内单胺类神经递质含量而改善CUMS大鼠的抑郁样行为。

Acteoside improves depression-like behaviors of CUMS rats by modulating BDNF-TrkB signaling pathway

AIM:To observe the effect of acteoside on depression-like behaviors of chronic unpredictable mild stress (CUMS) rats and to explore the mechanism involving brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) signaling pathway. METHODS:The depression-like rat model was established by CUMS combined with solitary rearing for 28 d. The model rats were randomly divided into 5 groups:model group, fluoxetine (20 mg/kg) group, and acteoside (30 mg/kg, 60 mg/kg and 120 mg/kg) groups, with 18 rats in each group. Another 18 normal rats served as control group. Acteoside, fluoxetine and normal saline were intragastrically given to the rats for 3 weeks. Forced swimming test and sugar preference test were carried out to detect the depression-like behaviors. Immunofluorescence technique was used to detect the expression of BDNF in the hippocampus. Western blot was conducted to determined the expression of TrkB in the hippocampus. The levels of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain of the rats were measured by ELISA. RESULTS:Compared with control group, the immobility time was obviously extended, while the sugar intake, the expression of BDNF and TrkB, and the 5-HT, DA and NE levels were apparently decreased in model group. After the rats were treated with fluoxetine and acteoside, all the above indicators were reversed, and the differences were statistically significant (P<0.05). CONCLUSION:Acteoside may improves depression-like behaviors of CUMS rats by upregulating BDNF-TrkB signaling activity and elevating 5-HT, DA and NE levels in the brain.