| 张付民,刘俊.柴胡疏肝散调节大鼠额叶环磷酸腺苷/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子信号通路发挥抗抑郁作用研究[J].安徽医药,2020,24(4):646-650. |
| 柴胡疏肝散调节大鼠额叶环磷酸腺苷/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子信号通路发挥抗抑郁作用研究 |
| Chaihu Shugan San exerts antidepressant effect by regulating the cAMP/CREB/BDNF signaling pathway in the prefrontal cortex of rats with chronic unpredictable mild stress |
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| DOI：10.3969/j.issn.1009?6469.2020.04.003 |
| 中文关键词: 抗抑郁药 柴胡疏肝散 抑郁 额叶前皮质 慢性不可预知温和应激 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信号转导通路 大鼠， Sprague?Dawley |
| 英文关键词: Antidepressive agents Chaihu shugan san Depression Prefrontal cortex Chronic unpredictable mild stress cAMP/CREB/BDNF transduction pathway Rats,sprague?dawley |
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| 中文摘要: |
| 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)。柴胡疏肝散组运动距离［( 400.29±40.24)cm比大鼠,(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)表达水平升高大，(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。 |
| 英文摘要: |
| Objective To explore the possible mechanism of Chaihu Shugan San against depression based on cyclic adenosine mo?nophosphate/cyclic adenosine monophosphate response element binding protein/brain derived neurotrophic factor(cAMP/CREB/ BDNF)signaling pathway.Methods According to the random number table，the experimental rats were assigned into blank group， model group，Escitalopram group and Chaihu Shugan San group from January 2017 to October 2018.In addition to the blank group， chronic unpredictable mild stress was used to develop depression models for other groups.The effects of Chaihu Shugan San on anti ?depression were evaluated by sucrose preference experiment，forced swimming test and open field experiment.The pathological changes of the prefrontal cortex(PFC)were observed by Nissl staining.The gene and protein expression levels of cAMP，CREB and BDNF in PFC were detected by Real time?PCR and Western bolt.Results Compared with the model group，after administration， the sugar and water preference rate in Chaihu Shugan San group increased［( 60.75±15.63)% vs.(77.39±18.39)%，P＝0.031)］， while the immobility time of forced swimming decreased［( 64.39±10.62)s vs.(47.93±18.71)s，P＝0.012)］ .the distance of move? ment in Chaihu Shugan San group［(400.29±40.24)vs.(502.59±36.13)cm，P＝0.000］and the number of times crossing the cen? tral area increased［(11.56±4.92)vs.(15.68±3.56)P＝0.011］，while the rest time decreased［(83.55±13.87)vs.(66.75±16.15) s，P＝0.028］.Nisslstainingshowedthattheshrinkage，and deep staining of Nissl body in cortex of rats in Chaihu Shugan San group were alleviated，and the decrease of dendrites was improved.Compared with the model group，after administration，the expres? sion levels of cAMP mRNA［( 0.37±0.16)vs.(0.53±0.16)P＝0.024］CREB mRNA［( 0.43±0.18)vs.(0.79±0.15)，P＝0.000］ and BDNF mRNA［(0.40±0.13)vs.(0.64±0.26)，P＝0.000］，inthePFC，of Chaihu Shugan San group were increased；the expres? sion levels of cAMP［(0.28±0.13)vs.(0.47±0.27)P＝0.000］CREB［(0.41±0.15)vs.(0.59±0.11)，P＝0.027］and BDNF pro?tein［( 0.43±0.11)vs.(0.58±0.15)，P＝0.022］inPFC，ofChaihu，Shugan San group were increased.Conclusion Chaihu Shugan San has anti?depressant effects，and its mechanism may be related to up?regulation of cAMP/CREB/BDNF signaling pathway. |
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