抑郁模型大鼠海马组织中内质网应激调控因子的表达及-细辛醚的干预作用

金铭; 蔡珍珍; 韩俊岩; 顾福灵; 林岩; 董海影; 宋晓明; 帅智峰; 何宝国; 沈云虹; 肖薇; 张晓杰

doi:10.13422/j.cnki.syfjx.2017080124

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抑郁模型大鼠海马组织中内质网应激调控因子的表达及-细辛醚的干预作用

药理 | 更新时间：2024-01-04

- 抑郁模型大鼠海马组织中内质网应激调控因子的表达及-细辛醚的干预作用
- Expression of Endoplasmic Reticulum Stress-regulating Factor in Hippocampus of Depressive Rats and Intervention of -Asarone
- 中国实验方剂学杂志 2017年23卷第8期页码：124-129
- 作者机构：
- 作者简介：
- 基金信息：
  
  黑龙江省科技厅攻关项目（PC13S06）
- DOI：10.13422/j.cnki.syfjx.2017080124
  中图分类号： R-332;R285.5
- 纸质出版日期：2017
- 稿件说明：
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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-细辛醚的干预作用[J]. 中国实验方剂学杂志, 2017,23(8):124-129.

JIN Ming, CAI Zhen-zhen, HAN Jun-yan, et al. Expression of Endoplasmic Reticulum Stress-regulating Factor in Hippocampus of Depressive Rats and Intervention of -Asarone[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(8): 124-129.
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-细辛醚的干预作用[J]. 中国实验方剂学杂志, 2017,23(8):124-129. DOI： 10.13422/j.cnki.syfjx.2017080124.

JIN Ming, CAI Zhen-zhen, HAN Jun-yan, et al. Expression of Endoplasmic Reticulum Stress-regulating Factor in Hippocampus of Depressive Rats and Intervention of -Asarone[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(8): 124-129. DOI： 10.13422/j.cnki.syfjx.2017080124.

摘要

目的：研究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，并探讨其相关的作用机制。方法：建立慢性轻度不可预见性应激刺激（CUMS）大鼠模型，将100只大鼠随机分为5组，分别为正常组，模型组，氟西汀组（10 mg·kg-1），β-细辛醚低剂量组（25 mg·kg-1）和高剂量组（50 mg·kg-1），每组20只，从造模第8天开始每天灌胃1次给药，连续21 d。于实验的第0天和第29天进行旷场实验；采用Nissl染色法观察各组大鼠海马组织神经元尼氏体的变化；实时荧光定量PCR（Real-time PCR）技术检测各组大鼠海马组织蛋白激酶R样内质网激酶（PERK），CCAAT/增强子结合蛋白同源蛋白（CHOP），钙网蛋白（CRT）mRNA表达情况；蛋白质免疫印迹（Western blot）技术检测各组大鼠海马组织PERK，CHOP，CRT蛋白表达。结果：经28 d慢性不可预见性温和刺激后，模型组大鼠与正常组大鼠比较，水平运动和垂直运动得分明显减少（P<0.05）；β-细辛醚低、高剂量组和氟西汀组大鼠与模型组比较，水平运动和垂直运动得分明显增加（P<0.05）。尼氏染色结果显示，模型组大鼠海马组织神经元细胞浆着色变浅，尼氏小体颗粒明显减少；β-细辛醚低、高剂量组大鼠海马区神经元形态相对较好，尼氏小体颗粒较模型组增多。模型组与正常组大鼠比较，PERK，CHOP，CRT mRNA表达上调（P<0.05），与模型组比较，β-细辛醚低、高剂量组和氟西汀组中PERK，CHOP，CRT mRNA表达明显下调（P<0.05）。与正常组比较，模型组大鼠PERK，CHOP，CRT蛋白表达均明显升高（P<0.05）；与模型组大鼠比较，氟西汀组、β-细辛醚低、高剂量组PERK，CHOP，CRT蛋白表达明显减少（P<0.05）。结论： β-细辛醚可能是通过调节海马内质网功能发挥抗抑郁作用。

Abstract

Objective: To study the expression of endoplasmic reticulum stress regulators in hippocampus of depressive rats and the intervention effect of β-asarone. Method: Totally 100 SD rats were randomly divided into five groups:the normal control group

the model group

the fluoxetine group (10 mg·kg-1)

the β-asarone low-dose group (25 mg·kg-1) and the high-dose group (50 mg·kg-1)

with 20 in each one. The depression model was established by CUMS. On the 8th day after modeling

rats in fluoxetine group and β-asarone group were treated with fluoxetine or β-asarone once daily through intragastric administration for 21 days (10 mg·kg-1·d-1 for the fluoxetine group

25 mg·kg-1·d-1 for the β-asarone low-dose group

50 mg·kg-1·d-1 for the β-asarone high-dose group). The open field test was carried out to assess the CUMS model and rats' ethological changes on the 0th and 29th day; The changes of nissl bodies in hippocampus neurons were observed by Nissl staining; The mRNA expressions of protein kinase R sample endoplasmic reticulum kinase(PERK)

CCAAT/EBP homologous protein(CHOP)

calprotectin(CRT) were tested by Real-time fluorescent quantitative PCR; The protein expressions of PERK

CHOP and CRT were detected by Western blot. Result: After CUMS for 28 days

scores of horizontal motion and vertical motion in model group were obviously lower than control group (P<0.05)

whereas those in β-asarone low-dose group

β-asarone high-dose group

fluoxetine group were higher model group (P<0.05). Nissl staining results showed that the color of neurons in control group became light

with less nissl bodies; β-asarone low-dose group

β-asarone high-dose group show more normal hippocampus neurons

with more Nissl bodies than model group. Compared with the model group

mRNA expressions of PERK

CHOP and CRT were up-regulated significantly in the model group

compared with control group (P<0.05); whereas those were down-regulated in β-asarone low dose group

β-asarone high dose group and fluoxetine group compared with the model group (P <0.05). Compared with the model group

protein expressions of PERK

CHOP and CRT were up-regulated significantly in the model group (P<0.05); whereas those were down-regulated in fluoxetine group

β-asarone low dose group

β-asarone high dose group (P<0.05). Conclusion: The antidepressant effect of β-asarone may be correlated with the regulation of endoplasmic reticulum functions.

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