Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats

Dai-yu XUE; Wen-jian BAO; You-ya LIANG; Xiao CHENG; Bi-yun XU

doi:10.13422/j.cnki.syfjx.20200503

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Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats

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- Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 9, Pages: 8-14(2020)
- 作者机构：
  
  1.广州中医药大学　中药学院，广州　 510006
  2.广州中医药大学　第二附属医院(广东省中医院)，广州　 510120
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200503
  CLC： R2-0; R22; R285.5; R289
- Received：23 August 2019，
  
  Published Online：19 November 2019，
  
  Published：05 May 2020
- 稿件说明：
移动端阅览
Dai-yu XUE, Wen-jian BAO, You-ya LIANG, et al. Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(9): 8-14.
DOI：

Dai-yu XUE, Wen-jian BAO, You-ya LIANG, et al. Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(9): 8-14. DOI： 10.13422/j.cnki.syfjx.20200503.

摘要

目的：

探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用，并探讨其可能的作用机制。

方法：

Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2.60，7.81，23.50 g·kg

-1

·d

-1

)。除正常组外，其余各组造成CUMS模型。每周称体质量，观察其行为学指标变化；实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30)，胞内磷脂酰肌醇激酶(PI3K)，环磷酸腺苷反应元件结合蛋白(CREB)，脑源性神经营养因子(BDNF) mRNA的表达；酶联免疫吸附测定(ELISA)检测血清中雌激素含量。

结果：

与正常组比较，模型组体质量、活动能力、兴趣等明显降低(

0.05，

0.01)；与模型组比较，六味地黄汤2.60，7.81，23.50 g·kg

-1

可明显提高CUMS大鼠糖水偏好度(

0.01)和旷场实验的站立次数(

0.01)；7.81，23.50 g·kg

-1

明显提高旷场实验的总距离(

0.05，

0.01)；2.60，7.81 g·kg

-1

可缩短水迷宫实验寻台潜伏期(

0.01)；7.81 g·kg

-1

可增加血清中雌激素含量(

0.05)；CUMS模型组大鼠海马组织内的GPR30，PI3K，CREB，BDNF mRNA表达明显下降(

0.05，

0.01)，六味地黄汤2.60 g·kg

-1

显著增加海马组织内的GPR30，CREB mRNA表达(

0.05，

0.01)，7.81 g·kg

-1

明显增加海马组织内的GPR30，PI3K，CREB，BDNF mRNA表达量(

0.05，

0.01)。

结论：

六味地黄汤具有抗抑郁作用，逆转CUMS大鼠抑郁样行为及学习记忆障碍，其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30，PI3K，CREB，BDNF mRNA表达有关。

Abstract

Objective:

To investigate the effect and possible mechanism of Liuwei Dihuangtang on memory impairment in rats with chronic depression.

Method:

Female Wistar rats were randomly divided into normal group (normal saline)

chronic unpredictable mild stress (CUMS) model group (normal saline)

and low

medium and high-dose Liuwei Dihuangtang groups (2.60

7.81

23.50 g·kg

-1

·d

-1

). Except for the normal group

all of the other groups were included in the chronic unpredictable mild stress model. Weight were measured every week

changes in their behavioral indicators were observed. The mRNA expressions of G protein-coupled estrogen receptor (GPR30)

phosphatidylinositol 3-kinase(PI3K)

cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the rat hippocampus were determined by real-time fluorescence quantification polymerase chain reaction (Real-time PCR). The concentration of serum estrogen was detected by enzyme-linked immunosorbent assay (ELISA) method.

Result:

Compared with normal group

model group showed decreases in weight

activity and interest. Liuwei Dihuangtang (2.60

7.81

23.50 g·kg

-1

) significantly increased the sucrose preference of CUMS rats (

0.01) and standing times in the open field test (

0.01)

doses of 7.81

23.50 g·kg

-1

significantly increased the total distance of the open field test (

0.05

0.01)

doses of 2.60

7.81 g·kg

-1

shortened the latency of water maze experiment (

0.01)

and dose of 7.81 g·kg

-1

increased serum estrogen concentration (

0.05). The mRNA expressions of GPR30

PI3K

CREB and BDNF in hippocampus of CUMS model group decreased significantly (

0.05

0.01)

but the mRNA expression levels of GPR30

CREB in hippocampus of 2.60 g·kg

-1

dose Liuwei Dihuangtang group increased significantly (

0.05

0.01)

and the mRNA expression levels of GPR30

PI3K

CREB

BDNF in hippocampus of 7.81 g·kg

-1

dose group increased significantly as well (

0.05

0.01).

Conclusion:

Liuwei Dihuangtang has effect in resisting depression

and reversing depression-like behavior and learning and memory impairment in CUMS rats

with the best effect in the medium-dose Liuwei Dihuangtang group. Its mechanism may be related to increase of serum estrogen and mRNA expressions of GPR30

PI3K

CREB and BDNF in rat hippocampus.

关键词

Keywords

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