运动联合抗抑郁药物对大鼠海马细胞和BDNF/pERK 信号通路的影响

目的 研究运动联合帕罗西汀的抗抑郁效果及其作用机制。方法 采用慢性不可预知性温和应激复制大鼠抑郁模型,分为对照组、模型组、运动组、给药组、联合组,每组12 只。通过规律性运动和帕罗西汀进行干预,用糖水和Morris 水迷宫实验检测大鼠行为学,作为缺乏快感的客观指标,判定模型是否复制成功。采用DCFH-DA 法检测海马细胞的凋亡率和活性氧（ROS）水平,Western blot 检测海马细胞中脑源性神经营养因子（BDNF）、磷酸化细胞外信号调节激酶（pERK）、神经肽（VGF）蛋白表达水平。结果 与对照组相比,联合组糖水消耗量降低,逃避潜伏期延长（P <0.05）;与运动组相比,联合组大鼠21 d 后糖水消耗量增加,逃避潜伏期降低（P <0.05）。与运动组相比,联合组细胞ROS、凋亡率降低（P <0.05）。模型组大鼠海马细胞中BDNF、pERK、VGF 蛋白表达低于对照组（P <0.05）;与运动组相比,联合组海马细胞中BDNF、pERK、VGF 蛋白表达升高。结论 运动联合帕罗西汀的抗抑郁效果优于单一运动疗法或药物治疗,可更好地缓解快感缺乏,降低海马细胞凋亡率和氧化应激损伤,其可能是通过BDNF/pERK 信号通路调控下游靶基因VGF 的表达而发挥作用。

Effect of exercise combined with antidepressants on hippocampalcells and BDNF/pERK signaling pathway in rats

Objective To study the antidepressive effect and mechanism of exercise combined withParoxetine. Methods Using the method of chronic unpredictable mild stress (CUMS), depression rat model wasprepared. The rats were divided into control group, model group, exercise group, Paroxetine group, and combination(exercise and Paroxetine) group. Through regular exercise and Paroxetine intervention, the behavior of the ratswas detected by sugar water and Morris water maze test, and used as an objective indicator of lack of pleasure todetermine whether the model was duplicated successfully or not. The apoptotic rate of hippocampal cells was detectedusing flow cytometry. The level of reactive oxygen species (ROS) was measured by DCFH-DA. The expression levelsof brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinases (pERK) andneuropeptide (VGF) were detected using Western blot. Results Compared with the control group, the consumptionof sugar water was significantly decreased and the escape latency was prolonged in the model group (P < 0.05).Compared with the exercise group, the consumption of sugar water significantly increased, the escape latency wassignificantly shortened in the combination group on the 21st d (P < 0.05). The ROS level and the apoptotic rate ofthe combination group were reduced compared to those of the exercise group (P < 0.05). The expressions of BDNF,pERK and VGF proteins in the hippocampal cells of the model group were significantly lower than those of the control group (P < 0.05). The expressions of BDNF, pERK and VGF proteins were significantly increased in the combination group compared with the exercise group (P < 0.05). Conclusions Paroxetine combined with exercise has better antidepressive effect than exercise therapy or drug therapy alone, can alleviate the lack of pleasure, and reduce oxidative stress injury and apoptosis rate in the hippocampal cells by regulating the expression of downstream target gene VGF through BDNF/pERK signaling pathway.