逍遥散拆方药队的抗抑郁作用及部分机制研究

Study on the antidepressant effects and mechanisms of composition drug-group of Xiaoyao Powder

目的:观察逍遥散的拆方药队(柴胡、当归、薄荷,简称柴当薄组)对CUMS抑郁模型小鼠行为学及5-HT1A/2A受体激动剂所引起的小鼠行为反应的影响,揭示该拆方药组的抗抑郁作用及5-HT/BDNF信号通路作用机制。方法:慢性不可预知温和应激+孤养6周制备CUMS小鼠抑郁模型,造模第3周逍遥散全方(30g/kg)、柴当薄组(16.43g/kg、21.90g/kg)、阿米替林(10mg/kg)开始灌胃给药,连续4周,以小鼠体重、自主活动量、糖水偏爱百分比、空间记忆探索能力等行为学指标评价抗抑郁作用。ELISA法测定模型小鼠血清BDNF、5-HT水平及海马部位5-HT含量,及采用8-OH-DPAT(5-HT1A受体激动剂)、DOI(5-HT2A受体激动剂)引起小鼠行为学变化实验,探讨作用机制。结果:与模型对照组比较,柴当薄组16.43g/kg、21.9g/kg剂量均显著提高CUMS模型小鼠的自主活动、糖水消耗量,明显缩短水迷宫测试中定位航行的潜伏期;柴当薄组16.43g/kg可显著增加空间探索实验时目标象限运动距离及有效区域进入次数。柴当薄组16.43g/kg、21.9g/kg显著增加模型小鼠血清BDNF、5-HT含量及海马部位5-HT水平,显著对抗DOI所致的小鼠甩头反应;柴当薄组21.9g/kg对8-OH-DPAT引起的小鼠5-HT样行为表现出明显的协同作用。结论:逍遥散功效拆方研究所获得的柴当薄药组对CUMS模型小鼠有良好的抗抑郁作用,并能协同8-OH-DPAT、拮抗DOI的作用,抗抑郁作用机制可能与激动5-HT1A受体、阻断5-HT2A受体从而影响5-HT/BDNF受体信号通路有关。

Objective： To observe the antidepressant effect of disassembled prescription drugs （ Chai Hu, Dang Gui and Bo He, referred as Chai Dang Bo drug-group） from Xiaoyao Powder in CUMS model mice, and the effects on the behavioral responses induced by 5-HT1A/2A ago- nists in mice, so as to investigate the antidepressant effect and the mechanism of 5-HT/BDNF signal pathway of Chai Dang Bo drug-group. Methods： The depression model in mice was prepared by using chronic unpredictable mild stress and isolated feeding for 6 weeks. On the third week,model mice were administrated intragastricly with Xiaoyao Powder （30g/kg）, Chai Dang Bo drug-group （16.43g/kg, 21.90g/ kg） and amitriptyline （10mg/kg） for 4 weeks. The body weight, autonomic activity, sucrose preference percentage, spatial memory ability in Morris test in CUMS model mice were observed to evaluate the antidepressant effect of Chai Dang Bo. The level of BDNF, 5-HT in serum and the content of 5-HT in hippocampus were detected by ELISA, and the behavioral responses induced by 8-OH-DPAT （5-HT1A receptor agonist） and DOI （5-HT2A receptor agonist） in mice were studied, so as to explain the mechanism of its action. Results： Compared with model group,Chai Dang Bo （16.43g/kg,21.90g/kg） could significantly increase the autonomic activities, sucrose consumption of CUMS model mice （ P 〈 0.01 ） , as well as short the escape latency in Morris test and increase the target quadrant motion distance and effective re- gional entry times in space exploration experiment （P 〈0.05）. Chai Dang Bo （16.43g/kg） significantly increased the level of BDNF, 5-HT in serum and the content of 5-HT in hippocampus in model mice （ P 〈0.01 ）. Chai Dang Bo （21.90g/kg） showed the synergistic effect with 8-OH-DPAT on 5-HT like behaviors in mice, and decreased the head twitch responses induced by DOI in mice. Conclusion： The Chai Dang Bo drug-group which comes from the antidepressant studying of effective composition of Xiaoyao Powder showed good antidepressant effect in CUMS model mice. It indicated that the mechanism of its antidepressant effect may be related to exciting 5-HT1A receptor, and blocking 5- HT2A receptor, that result in affecting the 5-HT/BDNF receptor signal transduction pathway.