越鞠丸石油醚部位潜在的快速抗抑郁作用与BDNF、TrkB蛋白表达的上调相关

Potent rapid antidepressant effects of petroleum ether fraction of Yueju pill associated with BDNF and TrkB up-regulation

目的研究越鞠丸石油醚部位是否具有快速抗抑郁潜力,并对其有效剂量及潜在的生物学机制进行了探讨。方法将44只昆明种♂小鼠随机分成空白组(生理盐水组)、越鞠丸石油醚部位(YJ-PE)高、中、低剂量组及氯胺酮组。单次给药后30 min对昆明小鼠进行小鼠悬尾行为绝望测试。再将24只昆明种♂小鼠分成空白组、筛选出有效的越鞠丸石油醚部位低剂量组和氯胺酮组,单次给药24 h后进行小鼠悬尾行为绝望测试。利用Western blot实验分别检测给药后30 min及24 h小鼠海马区BDNF和TrkB蛋白的表达变化。结果单次给药越鞠丸石油醚部位从30 min到24 h均能对其小鼠悬尾的行为绝望行为产生抗抑郁作用。给予越鞠丸石油醚部位30 min后小鼠海马中的BDNF及其受体TrkB的表达明显上调,且这种抗抑郁的作用机制可持续到24 h。结论越鞠丸石油醚部位(低剂量)具有快速抗抑郁的药物潜力,且这种潜在的快速抗抑郁作用与BDNF及其受体TrkB的激活相关。

Abstact: Aim To identify whether the petroleum ether fraction of Yueju pill( YJ-PE) could exhibit a potent rapid antidepressant effect and to investigate the underlying biological mechanism involved. Methods Fourty-four male KM mice were randomly assigned to five groups: the control group( saline group),low dosage of YJ-PE,middle dosage of YJ-PE,high dosage of YJ-PE and ketamine. After a single drug administration,we used tail suspension test( TST) to test the rapid antidepressant effect of YJ-PE in KM mice at30 min. Another twenty-four male KM mice were assinged to three groups: control group,screened effective low dosage of YJ-PE group and ketamine group. We usd TST to assess these mice at 24 h post a single administration. Western blot was performed to examine the expression of BDNF and TrkB in hippocampus of KM mice at 30 min and 24 h post a single administration. Results An acute administration of YJ-PE decreased the immobility time of KM mice in TST and increased the expression of BDNF and TrkB as soon as30 min post a single administration and lasted at least for 24 hours. Conclusion YJ-PE( low dosage) exhibits a rapid antidepressant-like potent,and the potent rapid antidepressant effects of YJ-PE are associated with the up-regulation of BDNF and TrkB.