基于均匀设计法评价柴胡-黄芩的配伍比例及抗抑郁机制

周丽萍; 李国春; 章宸一瑜; 赵凡; 李亚芹; 马世平; 瞿融

doi:10.13422/j.cnki.syfjx.20190451

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基于均匀设计法评价柴胡-黄芩的配伍比例及抗抑郁机制

配伍 | 更新时间：2021-02-09

- 基于均匀设计法评价柴胡-黄芩的配伍比例及抗抑郁机制
- Evaluation of Compatibility Proportion and Antidepressant Mechanism of Bupleuri Radix-Scutellariae Radix Based on Uniform Design
- 中国实验方剂学杂志 2019年25卷第13期页码：28-34
- 作者机构：
  
  1.南京中医药大学　基础医学院，医学与生命科学学院，南京　 210029；
  2.中国药科大学　中药学院，南京　 210038
- 作者简介：
  
  周丽萍，在读硕士，从事传统名方的配伍方法、作用机制和临床应用研究，E-mail：sherunlock@sina.com
  瞿融，教授，博士生导师，从事传统名方的配伍方法、作用机制和临床应用研究，Tel：025-85811065，E-mail：qurong@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81573701)
- DOI：10.13422/j.cnki.syfjx.20190451
  中图分类号： R22; R24; R28; C37; TS193
- 收稿日期：2018-08-21，
  
  网络出版日期：2018-11-03，
  
  纸质出版日期：2019-07-05
- 稿件说明：
移动端阅览
周丽萍, 李国春, 章宸一瑜, 等. 基于均匀设计法评价柴胡-黄芩的配伍比例及抗抑郁机制[J]. 中国实验方剂学杂志, 2019,25(13):28-34.

Li-ping ZHOU, Guo-chun LI, Chen-yi-yu ZHANG, et al. Evaluation of Compatibility Proportion and Antidepressant Mechanism of Bupleuri Radix-Scutellariae Radix Based on Uniform Design[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 28-34.
周丽萍, 李国春, 章宸一瑜, 等. 基于均匀设计法评价柴胡-黄芩的配伍比例及抗抑郁机制[J]. 中国实验方剂学杂志, 2019,25(13):28-34. DOI： 10.13422/j.cnki.syfjx.20190451.

Li-ping ZHOU, Guo-chun LI, Chen-yi-yu ZHANG, et al. Evaluation of Compatibility Proportion and Antidepressant Mechanism of Bupleuri Radix-Scutellariae Radix Based on Uniform Design[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 28-34. DOI： 10.13422/j.cnki.syfjx.20190451.

摘要

目的：

研究柴胡-黄芩药对发挥抗抑郁功效的最佳配伍比例，探讨其可能的抗抑郁机制。

方法：

取柴胡、黄芩在2015年版《中国药典》中的规定用量，按照二因素七水平均匀设计表进行配伍分组。采用慢性不可预见温和应激(CUMS)方法造模，抑郁症模型小鼠灌胃给予柴胡-黄芩不同配伍比例的水煎剂，观察其对模型小鼠糖水偏好、强迫游泳、悬尾、开野等行为学试验的影响。将所得数据进行回归分析，通过回归方程求解最佳配伍比例。对优选的配伍比例进行验证，并测定小鼠脑海马环磷腺苷反应元件结合蛋白(CREB)磷酸化的水平及脑源性神经营养因子(BDNF)的表达，探讨柴胡-黄芩药对可能的抗抑郁机制。

结果：

与空白组小鼠相比，模型组小鼠糖水偏好率显著降低(

0.01)，开野穿格次数显著减少(

0.01)，强迫游泳不动时间和悬尾不动时间显著延长(

0.01)；给予柴胡-黄芩水煎剂可增加模型小鼠的糖水偏好率(

0.05，

0.01)和穿格次数(

0.05，

0.01)，缩短强迫游泳不动时间和悬尾不动时间(

0.05，

0.01)。验证试验显示，柴胡与黄芩配伍后可改善模型小鼠抑郁样行为，增加小鼠的糖水偏好率(

0.01)，缩短强迫游泳不动时间和悬尾不动时间(

0.05，

0.01)；柴胡-黄芩(1∶1)配伍组及柴胡-黄芩(8∶3)配伍组均可显著增加模型小鼠穿格次数(

0.05，

0.01)；柴胡-黄芩(1∶1)配伍组在强迫游泳试验和悬尾试验中优于柴胡-黄芩(3∶8)和(8∶3)配伍组(

0.05，

0.01)，在糖水偏好试验和开野试验中显著优于柴胡-黄芩(3∶8)配伍组(

0.05)，且柴胡-黄芩(1∶1)配伍组促进海马中CREB磷酸化和增加海马中BDNF表达的效果最佳。

结论：

柴胡-黄芩药对可改善CUMS小鼠抑郁样行为，发挥抗抑郁功效，其最佳配伍比例为1∶1，最佳用量均约为5 g，其抗抑郁的作用机制可能与促进海马中CREB磷酸化和增加海马中BDNF表达有关。

Abstract

Objective:

To optimize proportion of couplet medicine of Bupleuri Radix and Scutellariae Radix in the treatment of anti-depression

and to explore the possible antidepressant mechanism of this couplet medicine.

Method:

The dosages of Bupleuri Radix and Scutellariae Radix in the 2015 edition of

Chinese Pharmacopoeia

were taken.According to U

) uniform design table

Bupleuri Radix and Scutellariae Radix were carried out into 7 groups.The chronic unpredictable mild depression model mice were induced by intragastric administration of decoction of this couplet medicine and the antidepressant effect was observed by the behavior tests

which included sucrose preference test

tail suspension test

forced swimming test and open field test(crossing scores). The regression equations were established by selecting the effective indexes.The experiments of retest were taken to check the results and the possible antidepressant mechanism was primarily investigated by measuring the phosphorylation level of cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) and expression of brain-derived neurotrophic factor(BDNF).

Result:

Compared with the blank group

sucrose preference rate of the model group was significantly decreased(

0.01)

the number of crossing was also obtained a significant decrease(

0.01) in the model group

the immobility times of forced swimming and tail suspension were prolonged obviously(

0.01) in the model group.The decoction of Bupleuri Radix-Scutellariae Radix could reverse the above indexes of model mice

the sucrose preference rate and the number of crossing were increased(

0.05

0.01)

the immobility times of forced swimming was evidently decreased(

0.01) and the immobility time of tail suspension was also decreased(

0.05

0.01). The experiment of retest showed that the decoction of Bupleuri Radix-Scutellariae Radix could improve depressive behavior of model mice

sucrose preference rates were significantly increased(

0.01)

the immobility time of forced swimming was significantly shorted(

0.01) and the time of tail suspension was also decreased(

0.05

0.01). The Bupleuri Radix-Scutellariae Radix(1∶1) and (8∶3) groups could increase the number of crossing (

0.05

0.01) of model mice

what's more

the Bupleuri Radix-Scutellariae Radix(1∶1) group was the most effective than the other groups and it could up-regulate phosphorylation levels of CREB and the expression of BDNF in the hippocampus.

Conclusion:

Compatibility of Bupleuri Radix and Scutellariae Radix can ameliorate depressive-like behavior of model mice

and the best antidepressant compatibility proportion of Bupleuri Radix and Scutellariae Radix is 1∶1

the optimal amounts of them are about 5 g. The antidepressant effect may relate to promoting phosphorylation level of CREB and the expression of BDNF in the hippocampus.

关键词

Keywords

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