抗抑郁药丙咪嗪对CREB/BDNF信号转导通路的影响Effects of Classical Antidepressant Imipramine on CREB / BDNF Signal Pathway
曾冰清,李亦文,刘永刚
ZENG Bingqing,LI Yiwen,LIU Yonggang
摘要(Abstract)：
目的研究经典三环类抗抑郁药丙咪嗪对环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子(CREB/BDNF)信号转导通路的影响。方法 40只昆明小鼠随机平均分成4组:对照组、丙咪嗪组、咯利普兰组、丙咪嗪+咯利普兰联合给药组。通过建立绝望状态下的抑郁模型,比较各组小鼠悬尾不动时间、强迫游泳不动时间以及在旷场实验中的自主活动情况。另30只昆明小鼠随机平均分成5组:对照组、应激组、丙咪嗪组、咯利普兰组、丙咪嗪+咯利普兰联合给药组,建立束缚应激的抑郁模型,采用Western blot方法比较各组小鼠海马内CREB的磷酸化水平(p CREB)、BDNF含量的变化。结果丙咪嗪、咯利普兰等单次给药显著缩短小鼠在悬尾、强迫游泳实验中的不动时间,而对各组小鼠在旷场实验中的表现无影响。丙咪嗪、咯利普兰显著升高应激小鼠海马内p CREB、BDNF含量。结论经典抗抑郁药改善抑郁样症状的作用有可能与增强p CREB/BDNF信号通路有关。
OBJECTIVE To investigate the effects of classical antidepressant imipramine on CREB / BDNF signal pathway.METHODS Forty KM mice were equally randomized into 4 groups: control group,imipramine-treated group,rolipram treatment group and drug combination( imipramine and rolipram) group. The antidepressant effects of these drugs were evaluated by behavioral performance tests,including tail suspension test( TST),forced swimming test( FST),open field test( OPF). In addition,50 KM mice were equally randomized into 5 groups: control group,stressed mice treated with vehicle,stressed mice treated with imipramine,stressed mice treated with rolipram and drug combination( imipramine and rolipram)-treated stressed group. The levels of p CREB,BDNF protein expression of hippocampus in mice were measured by western blot. RESULTS Imipramine and rolipram shortened the immobility time of mice in TST and FST significantly,but did not affect the performance in OPF. Results from western blot showed that imipramine and rolipram could elevate the level of p CREB and BDNF in stress mouse hippocampus significantly. CONCLUSION The classical antidepressant imipramine may exert its efficacy through CREB / BDNF signal pathway.
关键词(KeyWords)：
丙咪嗪;咯利普兰;小鼠;p CREB;BDNF
imipramine;rolipram;mice;p CREB;BDNF
基金项目(Foundation): 广东省科技计划项目(2012B061700110);; 广东省医院药学研究基金(奥赛康基金)(2014A22)
作者(Author):
曾冰清,李亦文,刘永刚
ZENG Bingqing,LI Yiwen,LIU Yonggang
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