Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3<italic style="font-style: italic">β</italic>/<italic style="font-style: italic">β</italic>-catenin in Hippocampus Tissue of Rats with Depression

Li-zhi SHANG; Meng-di MAO; Er-ping XU; Guo-qiang WANG; Yao-yang LI; Bao-guang LIU; Ming BA

doi:10.13422/j.cnki.syfjx.20202201

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Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression

Topic | 更新时间：2020-12-10

- Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 23, Pages: 12-19(2020)
- 作者机构：
  
  1.河南中医药大学中医药科学院，郑州 450046
  2.河南省仲景方药现代研究重点实验室，郑州 450046
  3.河南中医药大学基础医学院，郑州 450046
  4.河南中医药大学第一临床医学院，郑州 450006
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202201
  CLC： R2-0;R22;R285.5;R289
- Received：21 May 2020，
  
  Published Online：16 September 2020，
  
  Published：05 December 2020
- 稿件说明：
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尚立芝,毛梦迪,许二平等.柴胡加龙骨牡蛎汤对抑郁大鼠海马组织PI3K/Akt/GSK3β/β-catenin信号通路的影响[J].中国实验方剂学杂志,2020,26(23):12-19.

SHANG Li-zhi,MAO Meng-di,XU Er-ping,et al.Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(23):12-19.
尚立芝,毛梦迪,许二平等.柴胡加龙骨牡蛎汤对抑郁大鼠海马组织PI3K/Akt/GSK3β/β-catenin信号通路的影响[J].中国实验方剂学杂志,2020,26(23):12-19. DOI： 10.13422/j.cnki.syfjx.20202201.

SHANG Li-zhi,MAO Meng-di,XU Er-ping,et al.Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(23):12-19. DOI： 10.13422/j.cnki.syfjx.20202201.

摘要

目的

探讨柴胡加龙骨牡蛎汤对抑郁大鼠海马组织磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/糖原合成酶激酶3

（GSK3

）/

-链环蛋白（

-catenin）信号通路的影响。

方法

健康SD大鼠120只，随机取20只作为正常组，另100只大鼠用于制备慢性不可预见性温和应激（CUMS）抑郁模型。再将CUMS抑郁大鼠随机分为模型组，柴胡加龙骨牡蛎汤低、中、高剂量组，氟西汀组，每组20只。柴胡加龙骨牡蛎汤低、中、高剂量组分别灌胃3.25，6.5，13 g·kg

-1

；氟西汀组灌胃盐酸氟西汀10 mg·kg

-1

；正常组和模型组灌胃等量生理盐水；1次/d，共干预21 d。应用糖水偏好和强迫游泳实验评估抑郁行为，蛋白免疫印迹法（Western blot）检测各组大鼠大脑海马组织中PI3K，Akt，GSK3

以及

-catenin蛋白水平及其磷酸化水平。

结果

给药21 d后，与正常组比较，模型组糖水偏好显著下降（

0.01）；强迫游泳不动时间显著延长（

0.01）；PI3K，p-PI3K p110，p-PI3K p85蛋白水平均显著降低（

0.01）；Akt，p-Akt Thr308，p-Akt Ser473，p-GSK3

Ser9，

-catenin水平均显著降低（

0.01）；GSK3

，p-GSK3

Tyr216水平明显升高（

0.05，

0.01）。与模型组比较，柴胡加龙骨牡蛎汤中、高组大鼠糖水偏好显著增加（

0.01）；强迫游泳不动时间显著缩短（

0.01）；PI3K总蛋白，PI3K p110和PI3K p85亚基蛋白磷酸化水平均显著增高（

0.01）；p-Akt Thr308和p-Akt Ser473水平均显著升高（

0.01）；p-GSK3

Ser9，

-catenin水平显著增高（

0.01），而GSK3

，p-GSK3

Tyr216水平却明显降低（

0.05）。

结论

柴胡加龙骨牡蛎汤通过提高大鼠海马组织PI3K蛋白水平及活性，激活Akt，抑制GSK3

活性，阻止

-catenin降解，即提高大鼠海马组织PI3K/Akt信号通路活性，保护海马神经元。

Abstract

Objective

To study the effect of Chaihu Jia Longgu Mulitang on phosphatidylinositol-3-kinases （PI3K）/protein kinase B （Akt）/glycogen synthase kinase 3

（GSK3

）/

-catenin signaling pathway of hippocampus in rats with depression.

Method

A total of 120 SD rats were randomly divided into normal group，model group， and low， middle and high-dose Chaihu Jia Longgu Mulitang groups（3.25，6.5，13 g·kg

-1

）， and fluoxetine group， with 20 rats in each group. Except normal group， the depression model was prepared through chronic unpredictable mild stimulation（CUMS）. The normal group and the model group were given normal saline with 6.5 g·kg

-1

by gavage. Chaihu Jia Longgu Mulitang groups were intragastrically given corresponding herbal drugs 3.75，6.5，13 g·kg

-1

， while fluoxetine group was intragastrically given fluoxetine 10 mg·kg

-1

for 21 days， once a day. Then the depressive behaviors of rats were observed by sucrose preference test （SPT） and forced swimming test （FST）. Western blot was used to detect the protein expressions of PI3K，Akt，GSK3

and phosphorylation level.

Result

Compared with normal group，the sucrose preference index was decreased significantly，while the immobility time in FST was increased significantly（

0.01）， the protein expressions of PI3K， p-PI3K p110， p-PI3K p85 were decreased significantly

（

0.01）， and expressions of Akt， p-Akt Thr308，p-Akt Ser473， p-GSK3

Ser9 and

-catenin were decreased significantly（

0.01）， while the level of GSK3

， p-GSK3

Tyr216 were increased significantly in model group（

0.05，

0.01）. Compared with model group，Chaihu Jia Longgu Mulitang could increase sucrose preference index and decrease the immobility time in FST（

0.01）， the protein expressions of PI3K p110 and PI3K p85 was increased significantly （

0.01）， levels of Akt Thr308，Akt Ser473， p-GSK3

Ser9，

-catenin were increased significantly （

0.01）， whereas levels of GSK3

， and GSK3

Tyr216 were decreased significantly.

Conclusion

Chaihu Jia Longgu Mulitang could increase protein expression and activity of PI3K in rat hippocampus， activate Akt， inhibit GSK3

kinase activity and prevent

-catenin from degradation， so as to increase PI3K/Akt pathway activity in rat hippocampus， and protect hippocampal neurons.

关键词

Keywords

references

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Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression

DOI：10.13422/j.cnki.syfjx.20202201

摘要

Abstract

关键词

Keywords

references