六味地黄汤干预抑郁大鼠学习记忆的作用机制

薛岱榆; 包文健; 梁幼雅; 程骁; 徐碧云

doi:10.13422/j.cnki.syfjx.20200503

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六味地黄汤干预抑郁大鼠学习记忆的作用机制

经典名方 | 更新时间：2021-02-09

- 六味地黄汤干预抑郁大鼠学习记忆的作用机制
- Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats
- 中国实验方剂学杂志 2020年26卷第9期页码：8-14
- 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：
  
  [第一作者]　薛岱榆，在读硕士，从事中药抗衰老和调节内分泌临床与实验研究，E-mail: 564361827@qq.com
  *徐碧云，硕士，主治医师，从事中医睡眠医学和心理学研究，Tel：020-81499399-8486，E-mail: cloudxby@163.com
- 基金信息：
  
  国家自然科学基金青年基金项目(81603551)
- DOI：10.13422/j.cnki.syfjx.20200503
  中图分类号： R2-0; R22; R285.5; R289
- 纸质出版日期：2020-05-05，
  
  网络出版日期：2019-11-19，
  
  收稿日期：2019-08-23，
- 稿件说明：
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薛岱榆, 包文健, 梁幼雅, 等. 六味地黄汤干预抑郁大鼠学习记忆的作用机制[J]. 中国实验方剂学杂志, 2020,26(9):8-14.

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.
薛岱榆, 包文健, 梁幼雅, 等. 六味地黄汤干预抑郁大鼠学习记忆的作用机制[J]. 中国实验方剂学杂志, 2020,26(9):8-14. DOI： 10.13422/j.cnki.syfjx.20200503.

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

六味地黄汤慢性抑郁学习记忆雌激素脑源性神经营养因子

Keywords

Liuwei Dihuangtangchronic depressionlearning and memoryestrogenbrain-derived neurotrophic factor

references

美国研究发现抑郁会引发记忆问题[J]．世界最新医学信息文摘，2018，18(54)：29.

平军辉，崔桂梅，王萍．抑郁症患者治疗前后神经心理学测验变化分析[J]．临床心身疾病杂志，2011，17(17)：141-142.

张璐璐，郑洪波，邓悦，等．抑郁症患者治疗前后认知功能变化的分析[J]．神经疾病与精神卫生，2007，7(7)：262-265.

牛爱琴．六味地黄汤加减治疗绝经前后诸证48例临床研究[J]．亚太传统医药，2015，11(18)：129-130.

易健，刘柏炎，蔡光先．超微六味地黄汤对老年痴呆大鼠认知功能和脑组织碱性成纤维生长因子表达的影响[J]．中国实验方剂学杂志，2011，17(21)：139-142.

Q SU, Y CHENG, K JIN, et al. Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats[J].Exp Ther Med, 2016, 12(3): 1843-1848.

B C KARISETTY, P C JOSHI, A KUMARBC, et al. Sex differences in the effect of chronic mild stress on mouse prefrontal cortical BDNF levels: a role of major ovarian hormones[J].Neuroscience，2017, 356: 89-101.

Z LIU, Y QI, Z CHENG, et al. The effects of ginsenoside Rg1 on chronic stress induced depression-like behaviors, BDNF expression and the phosphorylation of PKA and CREB in rat[J].Neuroscience, 2016, 322: 358-369.

Y LUO, S KUANG, H LI, et al. cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress[J].Oncotarget, 2017, 8(22): 35558-35572.

C WANG, J GUO, R GUO. Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress[J].BMC Complement Altern Med, 2017, 17(1)：73.

李子雯，贾丹，党院霞，等．百合知母汤总皂苷调节5-HT功能治疗抑郁症的作用机制[J]．中国实验方剂学杂志，2018，24(19)：131-138.

金铭，蔡珍珍，韩俊岩，等．抑郁模型大鼠海马组织中内质网应激调控因子的表达及β-细辛醚的干预作用[J]．中国实验方剂学杂志，2017，23(8)：124-129.

P WINNER, A TOWELL, D SAMPSON, et al. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant[J].Psychopharmacology (Berl), 1987, 93(3)：358-364.

C QIBIN, R LI, M SU, et al. Changes in synaptic plasticity are associated with electroconvulsive shock-induced learning and memory impairment in rats with depression-like behavior[J].Neuropsychiatr Dis Treat, 2018, 14：1737-1746.

朱维煜，冯霞，王瑾，等．定志小丸对miR-16及5-HT重摄取的影响[J]．中国中药杂志，2018，43(17)：3513-3518.

牟雄军，明浩，许乐思，等．疏肝和胃汤抗抑郁作用有效物质部位筛选及其对海马内多种神经递质含量影响的研究[J]．中国中药杂志，2019，44(3)：526-534.

X Y LI, W W QI, Y X ZHANG, et al. Helicid ameliorates learning and cognitive ability and activities Camp/Pka/Creb signaling in chronic unpredictable mild stress rats [J].Biol Pharm Bull, 2019, 42 (7): 1146-1154.

R MARZIEH, M MEHDI, K AYAT, et al. Effect of crocin carotenoid on BDNF and CREB gene expression in brain ventral tegmental area of morphine treated rats[J].Asian Pac J Trop Biochem, 2018, 8(8): 387-393.

朱仲康，张林，柳春，等．补肾填精法对肾虚阿尔茨海默小鼠海马自噬的干预作用[J]．中国实验方剂学杂志，2019, 25(20)：43-48.

孙理军，孙瑜嬬，姜梅，等．补肾中药对肾虚质大鼠海马区ERK1表达的影响[J]．现代中医药，2018，38(6)：144-148.

沈政，林庶芝．颞叶皮层的认知功能[J]．生理科学进展，1993(1)：49-52.

D G JONES, R M DEVON. An ultrastructural study into the effects of pentobarbitone on synaptic organization[J].Brain Res, 1978, 147(1): 47-63.

罗俊，张科楠，肖帅，等．镇心省睡益智方及其精油对AD模型小鼠学习记忆的影响[J]．中国实验方剂学杂志，2019，25(9)：74-81.

王莹，杨硕，谢慧慧，等．二仙汤对去卵巢大鼠认知障碍的影响[J]．中国实验方剂学杂志，2018，24(17)：114-119.

唐明山．雌激素改善大鼠记忆及促进海马BDNF蛋白表达上调[J]．重庆医学，2012，41(23)：2386-2388，2391.

B C LIN, M SUZAWA, R D BLIND, et al. Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation[J].Cancer Res, 2009, 69: 5415-5423.

吴艳，卞慧敏．雌激素受体信号转导途径和功能[J]．安徽医药，2012，16(2)：242-244.

J E MALBERG, J A BLENDY. Antidepressant action: to the nucleus and beyond[J].Trends Pharmacol Sci, 2005, 26(12): 631-638.

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