桑菊解郁方对行为绝望模型和嗅球切除模型小鼠的抗抑郁作用及机制研究

沈鑫明; 张杨; 薛瑞; 罗亚; 李硕; 李劲草; 苏瑞斌; 张有志

doi:10.3969/j.issn.1006-2157.2023.10.009

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桑菊解郁方对行为绝望模型和嗅球切除模型小鼠的抗抑郁作用及机制研究

实验研究 | 更新时间：2023-11-06

- 桑菊解郁方对行为绝望模型和嗅球切除模型小鼠的抗抑郁作用及机制研究
- Study on antidepressant effect and mechanism of Sangju Jieyu Formula on behavioral despair mouse model and on olfactory bulbectomized mouse model
- 北京中医药大学学报 2023年46卷第10期页码：1382-1390
- 作者机构：
  
  1.南京中医药大学　南京　210046
  2.军事科学院军事医学研究院毒物药物研究所，抗毒药物与毒理学国家重点实验室
  3.安徽理工大学医学院
- 作者简介：
  
  沈鑫明，男，在读硕士生
  # 张有志，男，博士，研究员，博士生导师，主要研究方向：神经精神药理学，E-mail: bcczyz@163.com
- 基金信息：
  
  国家自然科学基金项目(81274117)
- DOI：10.3969/j.issn.1006-2157.2023.10.009
  中图分类号： R285.5
- 纸质出版日期：2023-10-30，
  
  网络出版日期：2023-09-28，
  
  收稿日期：2023-04-06，
- 稿件说明：
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沈鑫明, 张杨, 薛瑞, 等. 桑菊解郁方对行为绝望模型和嗅球切除模型小鼠的抗抑郁作用及机制研究[J]. 北京中医药大学学报, 2023,46(10):1382-1390.

SHEN Xinming, ZHANG Yang, XUE Rui, et al. Study on antidepressant effect and mechanism of Sangju Jieyu Formula on behavioral despair mouse model and on olfactory bulbectomized mouse model[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023,46(10):1382-1390.
沈鑫明, 张杨, 薛瑞, 等. 桑菊解郁方对行为绝望模型和嗅球切除模型小鼠的抗抑郁作用及机制研究[J]. 北京中医药大学学报, 2023,46(10):1382-1390. DOI： 10.3969/j.issn.1006-2157.2023.10.009.

SHEN Xinming, ZHANG Yang, XUE Rui, et al. Study on antidepressant effect and mechanism of Sangju Jieyu Formula on behavioral despair mouse model and on olfactory bulbectomized mouse model[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023,46(10):1382-1390. DOI： 10.3969/j.issn.1006-2157.2023.10.009.

摘要

目的

探讨药食同源中药复方桑菊解郁方的抗抑郁作用及潜在作用机制。

方法

(1)行为绝望模型实验。通过悬尾、强迫游泳和自发活动复制模型。将小鼠分为对照组，度洛西汀组(悬尾实验10 mg/kg，强迫游泳及自发活动实验各20 mg/kg)，桑菊解郁方低、中、高剂量组(267.4、534.8、1 069.5 mg/kg)，评价桑菊解郁方单次灌胃给药的抗抑郁作用。(2)嗅球切除模型实验。将小鼠分为假手术组，模型组，度洛西汀组(10 mg/kg)，桑菊解郁方中、高剂量组(534.8、1 069.5 mg/kg)，灌胃给药15 d，采用毛发评估实验、自发活动实验和悬尾实验评价桑菊解郁方的抗抑郁作用，并采用ELISA检测各组小鼠海马组织丙二醛(MDA)、超氧化物歧化酶(SOD)含量，采用蛋白质印迹法检测小鼠海马胱天蛋白酶3(CASP3)和突触后致密蛋白95(PSD－95)蛋白表达水平。

结果

(1)在行为绝望模型实验中，单次灌胃高剂量桑菊解郁方及度洛西汀可缩短小鼠悬尾不动时间(

0.05)，单次灌胃各剂量桑菊解郁方及度洛西汀可缩短小鼠游泳不动时间(

0.05)，且在有效剂量范围内对中枢神经系统无兴奋和抑制作用。(2)在小鼠嗅球切除模型实验中，与假手术组比较，模型组小鼠自发活动增多、悬尾不动时间增长、毛发评分下降(均

0.05)；小鼠海马组织中MDA含量增加，SOD含量下降(均

0.05)；CASP3蛋白表达增加，PSD－95蛋白表达减少(均

0.05)。与模型组比较，高剂量桑菊解郁方组和度洛西汀组上述改变均被逆转(均

0.05)。

结论

桑菊解郁方具有抗抑郁作用，其作用机制可能与抗氧化应激、抗海马细胞凋亡和增强突触可塑性有关。

Abstract

Objective

We aimed to evaluate the antidepressant effect of the Chinese medical compound formula—

Sangju Jieyu

Formula (SJJY) and the underlying mechanism.

Methods

(1) Behavioral despair model experiment. The model was established through tail suspension

forced swimming and spontaneous locomotro activity. Mice were divided into the control group

the duloxetine group (10 mg/kg in the tail suspension test [TST]

20 mg/kg in the forced swimming test [FST] and the spontaneous locomotor activity test [SLAT] )

and the SJJY groups (267.4

534.8

and 1 069.5 mg/kg). The antidepressant activity of a single intragastric administration of SJJY was evaluated by conducting the TST

FST

and SLAT. (2) Olfactory bulbectomized (OB) model experiment. Mice were divided into the sham-operation group

the model group

the duloxetine (10 mg/kg) group

and the SJJY groups (534.8 and 1 069.5 mg/kg). Duloxetine and SJJY were administered intragastrically for 15 days. The coat state test (CST)

SLAT

and TST were conducted to evaluate the antidepressant activity of SJJY when administered multiple times

and ELISA was used to detect the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in hippocampal tissues. Western blotting was conducted to determine the hippocampal expression levels of caspase-3(CASP3) and post synaptic density 95(PSD-95).

Results

(1) In the behavioral despair experiment

a single dose of SJJY (1 069.5 mg/kg) or duloxetine (10 mg/kg) significantly shortened the suspension immobility time (

0.01)

and a single dose of SJJY (267.4

534.8

or 1 069.5 mg/kg) or duloxetine (20 mg/kg) significantly shortened the swimming immobility time (

0.05). These effective doses had no excitatory or inhibitory effect on the central nervous system. (2) In the OB model experiment

compared with the model group

administration of SJJY (1 069.5 mg/kg) reversed OB-induced elevated spontaneous activity

increased the TST immobility time

decreased the coat state score (all

0.05)

upregulated hippocampal MDA levels

downregulated SOD levels (both

0.05)

upregulated hippocampal CASP3 protein levels

and downregulated PSD-95 protein levels (both

0.05).

Conclusion

SJJY has antidepressant activity. Its mechanism of action may be related to oxidative stress

anti-hippocampal apoptosis

and enhanced synaptic plasticity.

关键词

桑菊解郁方药食同源抗抑郁行为绝望模型嗅球切除模型氧化应激细胞凋亡小鼠

Keywords

Sangju Jieyu Formulahomology of medicine and foodantidepressantbehavioral despair modelolfactory bulbectomized modeloxidative stressapoptosismice

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