目的基于环磷酸腺苷/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子(cAMP/CREB/BDNF)信号转导通路信号通路探讨柴胡疏肝散抗抑郁的可能机制。方法2017年1月至2018年10月,采用随机数字表法将实验大鼠分为空白组、模型组、艾司西酞普兰...目的基于环磷酸腺苷/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子(cAMP/CREB/BDNF)信号转导通路信号通路探讨柴胡疏肝散抗抑郁的可能机制。方法2017年1月至2018年10月,采用随机数字表法将实验大鼠分为空白组、模型组、艾司西酞普兰组和柴胡疏肝散组,除空白组外,其他各组采用慢性不可预知温和应激制定抑郁症模型。用蔗糖偏好实验、强迫游泳实验和旷场实验实验评价柴胡疏肝散抗抑郁的作用。用尼氏染色观察大鼠前额叶皮层区病理形态变化。用Real time PCR和蛋白质印迹法检测大鼠前额叶皮层中cAMP、CREB、BDNF的基因和蛋白表达水平。结果给药后,与模型组比较,柴胡疏肝散大鼠糖水偏好率有所增加[(60.75±15.63)%比(77.39±18.39)%,P=0.031],而大鼠强迫游泳不动时间[(64.39±10.62)s比(47.93±18.71)s,P=0.012],均差异有统计学意义(P<0.05)。柴胡疏肝散组大鼠运动距离[(400.29±40.24)cm比(502.59±36.13)cm]和穿越中央区域次数[(11.56±4.92)比(15.68±3.56)]增加(P=0.000,P=0.011),静止时间[(83.55±13.87)s比(66.75±16.15)s,P=0.028],均差异有统计学意义。尼氏染色显示柴胡疏肝散组大鼠皮层尼氏体固缩和深染减轻,树突减少情况好转。柴胡疏肝散组大鼠PFC中cAMP、CREB、BDNF mRNA(0.53±0.16、0.79±0.15、0.64±0.26)表达水平升高(0.37±0.16、0.43±0.18、0.40±0.13)(P=0.024,P=0.000,P=0.000),均差异有统计学意义。柴胡疏肝散组大鼠PFC中cAMP、CREB、BDNF蛋白(0.47±0.27、0.59±0.11、0.58±0.15)表达水平升高(0.28±0.13、0.41±0.15、0.43±0.11)(P=0.000,P=0.027,P=0.022)。结论柴胡疏肝散具有抗抑郁的作用,其机制可能与其上调cAMP/CREB/BDNF信号通路有关。展开更多
This article reviewed the beneficial effects of moderate voluntary physical exercise on brain health according to the studies on humans and animals, which includes improving psychological status and cognitive function...This article reviewed the beneficial effects of moderate voluntary physical exercise on brain health according to the studies on humans and animals, which includes improving psychological status and cognitive function, enhancing psychological well-being, decreasing the risks of Alzheimer＇s disease （AD） and dementia, and promoting the effects of antidepressant and anxiolytic. The possible underlying neurobiological mechanisms are involved up-active and down-active pathways. The up-active pathway is associated with enhancements of several neurotransmitters systems afferent to hippocampus, including norepinephrine （NE）, serotonin （5-Hydroxytryptamine, 5-HT）, acetylcholine （ACh） and γ-aminobutyric acid （GABA）. The down-active pathway is mainly concerned with up-regulation of the brain-derived neurotrophic factor （BDNF） and neurogenesis. It is suggested that NE activation via β-adrenergic receptors may be essential for exercise-induced BDNF up-regulation. The possible intracellular signaling pathways of NE-mediated BDNF up-expression may be involved in GPCR-MAPK-PI-3K crosstalk and positive feedback.展开更多
文摘目的基于环磷酸腺苷/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子(cAMP/CREB/BDNF)信号转导通路信号通路探讨柴胡疏肝散抗抑郁的可能机制。方法2017年1月至2018年10月,采用随机数字表法将实验大鼠分为空白组、模型组、艾司西酞普兰组和柴胡疏肝散组,除空白组外,其他各组采用慢性不可预知温和应激制定抑郁症模型。用蔗糖偏好实验、强迫游泳实验和旷场实验实验评价柴胡疏肝散抗抑郁的作用。用尼氏染色观察大鼠前额叶皮层区病理形态变化。用Real time PCR和蛋白质印迹法检测大鼠前额叶皮层中cAMP、CREB、BDNF的基因和蛋白表达水平。结果给药后,与模型组比较,柴胡疏肝散大鼠糖水偏好率有所增加[(60.75±15.63)%比(77.39±18.39)%,P=0.031],而大鼠强迫游泳不动时间[(64.39±10.62)s比(47.93±18.71)s,P=0.012],均差异有统计学意义(P<0.05)。柴胡疏肝散组大鼠运动距离[(400.29±40.24)cm比(502.59±36.13)cm]和穿越中央区域次数[(11.56±4.92)比(15.68±3.56)]增加(P=0.000,P=0.011),静止时间[(83.55±13.87)s比(66.75±16.15)s,P=0.028],均差异有统计学意义。尼氏染色显示柴胡疏肝散组大鼠皮层尼氏体固缩和深染减轻,树突减少情况好转。柴胡疏肝散组大鼠PFC中cAMP、CREB、BDNF mRNA(0.53±0.16、0.79±0.15、0.64±0.26)表达水平升高(0.37±0.16、0.43±0.18、0.40±0.13)(P=0.024,P=0.000,P=0.000),均差异有统计学意义。柴胡疏肝散组大鼠PFC中cAMP、CREB、BDNF蛋白(0.47±0.27、0.59±0.11、0.58±0.15)表达水平升高(0.28±0.13、0.41±0.15、0.43±0.11)(P=0.000,P=0.027,P=0.022)。结论柴胡疏肝散具有抗抑郁的作用,其机制可能与其上调cAMP/CREB/BDNF信号通路有关。
基金the National Natural Science Fundation of China (No. 30570895,No. 30700389)
文摘This article reviewed the beneficial effects of moderate voluntary physical exercise on brain health according to the studies on humans and animals, which includes improving psychological status and cognitive function, enhancing psychological well-being, decreasing the risks of Alzheimer＇s disease （AD） and dementia, and promoting the effects of antidepressant and anxiolytic. The possible underlying neurobiological mechanisms are involved up-active and down-active pathways. The up-active pathway is associated with enhancements of several neurotransmitters systems afferent to hippocampus, including norepinephrine （NE）, serotonin （5-Hydroxytryptamine, 5-HT）, acetylcholine （ACh） and γ-aminobutyric acid （GABA）. The down-active pathway is mainly concerned with up-regulation of the brain-derived neurotrophic factor （BDNF） and neurogenesis. It is suggested that NE activation via β-adrenergic receptors may be essential for exercise-induced BDNF up-regulation. The possible intracellular signaling pathways of NE-mediated BDNF up-expression may be involved in GPCR-MAPK-PI-3K crosstalk and positive feedback.
