耳甲电针对抑郁模型大鼠海马Raf/ERK/RSK/CREB信号通路的影响

李少源; 荣培晶; 高国建; 张悦; 王俊英; 王瑜; 李亮; 张金铃; 国笑

doi:10.13702/j.1000-0607.190292

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耳甲电针对抑郁模型大鼠海马Raf/ERK/RSK/CREB信号通路的影响

机制探讨 | 更新时间：2023-08-11

- 耳甲电针对抑郁模型大鼠海马Raf/ERK/RSK/CREB信号通路的影响
- Auricular electroacupuncture improves depression possibly by promoting hippocampal Raf/ERK/RSK/CREB signaling in chronic unpredictable mild stress induced depression rats
- 针刺研究 2019年44卷第8期页码：554-559
- 作者机构：
  
  1. 中国中医科学院针灸研究所
  2. 中国中医科学院
- 作者简介：
- 基金信息：
  
  北京市科委脑认知与脑医学专项（No.Z161100002616003）;国家重点研发计划项目（No.2018YFC1705800）;中国中医科学院针灸研究所基本科研业务费自主选题项目（No.201814002）;国家自然科学基金面上项目（No.81473780）;中德合作研究项目（No.GZ1236）;中国中医科学院中医药“一带一路”合作专项课题（No.GH2017-07）;广东省珠江学者计划（No.A1-AFD018181Z3905）
- DOI：10.13702/j.1000-0607.190292
  中图分类号：
- 纸质出版日期：2019
- 稿件说明：
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李少源, 荣培晶, 高国建, 等. 耳甲电针对抑郁模型大鼠海马Raf/ERK/RSK/CREB信号通路的影响[J]. 针刺研究, 2019,44(8):554-559.

LI Shao-yuan, RONG Pei-jing, GAO Guo-jian, et al. Auricular electroacupuncture improves depression possibly by promoting hippocampal Raf/ERK/RSK/CREB signaling in chronic unpredictable mild stress induced depression rats[J]. Acupuncture research, 2019, 44(8): 554-559.
李少源, 荣培晶, 高国建, 等. 耳甲电针对抑郁模型大鼠海马Raf/ERK/RSK/CREB信号通路的影响[J]. 针刺研究, 2019,44(8):554-559. DOI： 10.13702/j.1000-0607.190292.

LI Shao-yuan, RONG Pei-jing, GAO Guo-jian, et al. Auricular electroacupuncture improves depression possibly by promoting hippocampal Raf/ERK/RSK/CREB signaling in chronic unpredictable mild stress induced depression rats[J]. Acupuncture research, 2019, 44(8): 554-559. DOI： 10.13702/j.1000-0607.190292.

摘要

目的:观察耳甲电针对慢性不可预知性温和刺激(CUMS)诱导的抑郁大鼠海马细胞外信号调节激酶(ERK)信号转导通路的影响

探讨耳甲电针抗抑郁效应的机制。方法:SD大鼠随机分为空白组、模型组、耳甲电针组、PD98059抑制剂(PD)组、二甲基亚砜(DMSO)组、PD+耳甲电针组

每组10只。采用孤养结合连续21 d CUMS方法制备抑郁大鼠模型。耳甲电针组、PD+耳甲电针组于耳甲区的"心"和"神门"耳穴给予连续28 d电针刺激

每天30 min;PD组、DMSO组、PD+耳甲电针组分别给予连续28 d侧脑室注射PD98059、DMSO、PD98059

每只5μL/d。记录造模前后、干预后各组大鼠糖水消耗量。采用Western blot法检测干预后各组大鼠海马Raf、p-Raf、ERK、p-ERK、RSK、CREB、p-CREB蛋白的相对表达量。结果:与空白组比较

模型组大鼠糖水消耗量及海马Raf、p-Raf、ERK、p-ERK、RSK、CREB、p-CREB均显著降低(P<0. 01)。与模型组比较

耳甲电针组大鼠糖水消耗量及海马Raf、p-Raf、ERK、p-ERK、RSK、CREB、pCREB均显著升高(P<0. 05

P<0. 01)

PD+耳甲电针组p-Raf、ERK、CREB明显升高(P<0. 01

P<0. 05)

PD组p-ERK明显下降(P<0. 05)。与耳甲电针组比较

PD+耳甲电针组p-ERK、RSK和pCREB明显下降(P<0. 05

P<0. 01)。结论:海马内Raf/ERK/RSK/CREB信号通路可能参与了耳甲电针的抗抑郁效应

且该效应在一定程度上可被ERK阻断剂所抑制。

Abstract

Objective To observe the effect of auricular electroacupuncture(EA)on intracellular Raf/extracellular signal-regulated kinase(ERK)/ribosomal S6 kinase(RSK)/cAMP response element-binding protein(CREB)signal pathway in the hippocampus of depression model rats

so as to explore its anti-depressive mechanism.Methods A total of 60 male SD rats were randomly divided into control

model

auricular EA

PD98059(ERK inhibitor)

DMSO(Dimethylsulfoxide)

PD98059+EA groups(n=10 in each group). The rats in the control group were fed with normal diet without any treatment. The depression model was induced by chronic unpredictable mild stress(CUMS)for consecutive21 days. EA(20 Hz

2 mA)was applied to bilateral auricular"Xin"(Heart)and"Shenmen"for 30 min

once daily for28 days. Rats of the PD98059

DMSO and PD98059+EA groups received intracerebroventricular injection of PD98059(100 μmol/L)

DMSO and PD98059(dissolved by DMSO)solutions(5 μL/d)

respectively

once daily for 28 days.Sucrose preference test(sucrose consumption)was conducted at the baseline

before and after the intervention. The expression of hippocampal Raf

phosphorylated(p)-Raf

ERK

p-ERK

RSK

CREB and p-CREB proteins were detected by Western blot after EA intervention.Results Following modeling

the sucrose consumption volume

and the expression levels of hippocampal Raf

p-Raf

ERK

p-ERK

RSK

CREB

p-CREB proteins were significantly lower in the model group than those in the control group(P<0. 01). Following the treatment

the sucrose consumption and the expression levels of Raf

p-Raf

ERK

p-ERK

RSK

CREB

p-CREB in the auricular EA group and those of p-Raf

ERK and CREB in the PD98059+EA group were obviously increased in comparison with the model group(P<0. 05

P<0. 01)

the expression level of p-ERK in the PD98059 group was obviously decreased in comparison with the model group(P<0. 05)

suggesting an improvement of depression after auricular EA. Compared with auricular EA group

the expression level of p-ERK

p-CREB and RSK in the PD98059+EA group were significantly decreased(P<0. 05).Conclusion EA of auricular"Xin"and"Shenmen"is able to improve depression in depression rats

which is probably related to its effect in promoting activities of hippocampal Raf/ERK/RSK/CREB signaling.

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