【摘要】 目的观察20(S)-原人参二醇对焦虑模型小鼠抗焦虑作用,并探讨其药理学机制。方法用对1-(3-氯苯基)哌嗪单盐酸盐(mCPP)诱导焦虑的方法进行造模,采用高架十字迷宫和明暗箱实验,对20(S)-原人参二醇进行抗焦虑作用观察,并与抗焦虑药地西泮(DXP)的作用进行比较。观察20(S)-原人参二醇对焦虑小鼠的行为学,脑组织分区若干基因表达丰度,脑组织分区BDNF和p-CREB表达丰度及脑组织神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)含量的影响。结果高架十字迷宫(EPM)和明暗箱行为学观察表明,20(S)-原人参二醇可明显提高小鼠在迷宫中的开臂访问次数、时间和跑动距离,也可明显提高小鼠在明暗箱的明箱中的访问次数和停留时间。与模型组比较,20(S)-原人参二醇可显著降低小鼠脑组织5-HT、NE和DA的含量,能增加小鼠丘脑、海马BDNF、TrkB、GR、PKA、CREB的基因表达,增加小鼠大脑皮质TrkB、CREB的基因表达,降低小鼠大脑皮质CRH及其受体基因的表达,增加小鼠丘脑和海马中BDNF和p-CREB蛋白的表达。结论 20(S)-原人参二醇具有明显抗焦虑作用,其作用机制可能和调节脑组织神经递质含量以及调控PKA-CREB-BDNF信号通路有关。更多还原

【Abstract】 AIM To observe the anti anxiety effects of 20(S)-protopanaxadiol on the anxiety model mice,and to investigate its pharmacological mechanism.METHODS 1-(3-chlorophenyl)piperazine monohydrochloride(mCPP)was used to make the anxiety model mice.The elevated plus-maze test(EPM)and the light-dark box test were used to observe the anti anxiety effect of 20(S)-protopanaxadiol,compared with diazepam.The ethology of anxiety mice,the expression of certain genes in brain tissues,the expression of BDNF and p-CREB proteins in brain tissues and the content of brain neurotransmitter-serotonin(5-HT),norepinephrine(NE)and dopamine(DA)were observed after the using of 20(S)-protopanaxadiol.RESULTS The observation of ethology indicated that 20(S)-protopanaxadiol can significantly improve the visits,time,and running distances in the open arms of EPM,and also can significantly improve the visits and residence time in the light box.Compared with the model group,20(S)-protopanaxadiol significantly reduced the content of 5-HT,NE and DA in the brain tissues of mice.Compared with the model group,20(S)-protopanaxadiol can increase the gene expression in the hypothalamus and hippocampus of mice,such as BDNF,TrkB,GR,PKA,CREB.It also can increase the gene expression in the cerebral cortex of mice,such as TrkBand CREBand reduce the gene expression of CRHand its receptor.And 20(S)-protopanaxadiol can increase the expression of BDNF and p-CREB in the hypothalamus and hippocampus of mice.CONCLUSION 20(S)-protopanaxadiol has the distinct effect of anti anxiety.The mechanisms are probably related with regulating the content of neurotransmitters in the brain.And the molecular mechanisms are probably related with the PKA-CREB-BDNF signaling pathway.更多还原