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

您当前的位置：

首页 >

文章列表页 >

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
- 收稿日期：2023-04-06，
  
  网络出版日期：2023-09-28，
  
  纸质出版日期：2023-10-30
- 稿件说明：
移动端阅览
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

Keywords

references

MALHI GS , MANN JJ . Depression [J]. Lancet , 2018 , 392 ( 10161 )： 2299 － 2312 .

LU J , XU X , HUANG Y , et al . Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study [J]. Lancet Psychiatry , 2021 , 8 ( 11 ): 981 － 990 .

BERTON O , NESTLER EJ . New approaches to antidepressant drug discovery: beyond monoamines [J]. Nat Rev Neurosci , 2006 , 7 ( 2 ): 137 － 151 .

唐启盛 . 抑郁障碍中西医研究进展述评 [J]. 北京中医药大学学报， 2022 , 45 ( 9 ): 871 － 877 .

BULLOCH AGM , PATTEN SB . Non-adherence with psychotropic medications in the general population [J]. Soc Psychiatry Psychiatr Epidemiol , 2010 , 45 ( 1 ): 47 － 56 .

SHARMA R , KABRA A , RAO MM , et al . Herbal and holistic solutions for neurodegenerative and depressive disorders: leads from Ayurveda [J]. Curr Pharm Des , 2018 , 24 ( 22 ): 2597 － 2608 .

孙文军，李小黎，徐向青，等 . 基于云数据的中医药方案降低抑郁障碍远期复发率的大样本、多中心、前瞻性队列研究 [J]. 北京中医药大学学报， 2022 , 45 ( 9 )： 890 － 896 .

中华中医药学会心身医学分会专家组．舒肝解郁胶囊治疗轻中度抑郁障碍临床应用专家共识 [J]. 北京中医药大学学报， 2021 , 44 ( 11 )： 969 － 977 .

李囿松，呼亚玲，申静，等 . 巴戟天寡糖胶囊治疗广泛人群下急性发作期轻中度抑郁症的Ⅳ期临床研究 [J]. 中药药理与临床， 2022 , 38 ( 4 ): 136 － 139 .

谷春华，任君霞，杨立波，等 . 解郁除烦胶囊治疗抑郁症334例多中心随机双盲对照试验 [J]. 中医杂志， 2016 , 57 ( 15 ): 1297 － 1302 .

李成功，孙新明，胡时先，等 . 一种评价抗抑郁中药组合物在治疗轻、中度抑郁症中有效性和安全性的方法： CN103230602A [P] . 2013－08－07 .

DOME P , TOMBOR L , LAZARY J , et al . Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review [J]. Brain Res Bull , 2019 , 146 : 51 － 78 .

SARRIS J , LOGAN AC , AKBARALY TN , et al . International Society for Nutritional Psychiatry Research consensus position statement: nutritional medicine in modern psychiatry [J]. World Psychiatry ， 2015 , 14 ( 3 ): 370 － 371 .

苏伟，万聆，简素平，等 . 桑叶总黄酮提取纯化工艺及抗氧化性研究 [J]. 食品工业科技， 2020 , 41 ( 10 ): 151 － 156 .

王婷婷，王少康，黄桂玲，等 . 菊花主要活性成分含量及其抗氧化活性测定 [J]. 食品科学， 2013 , 34 ( 15 ): 95 － 99 .

刘鹏，李达，纪海玉，等 . 枸杞多糖的提取及其体外抗氧化活性 [J]. 食品研究与开发， 2022 , 43 ( 10 ): 111 － 116 .

FREITAS AE , MACHADO DG , BUDNI J , et al . Fluoxetine modulates hippocampal cell signaling pathways implicated in neuroplasticity in olfactory bulbectomized mice [J]. Behav Brain Res , 2013 , 237 ： 176 － 184 .

STERU L , CHERMAT R , THIERRY B , et al . The tail suspension test: A new method for screening antidepressants in mice [J]. Psychopharmacology , 1985 , 85 ( 3 )： 367 － 370 .

CAN A , DAO DT , ARAD M , et al . The mouse forced swim test [J/OL]. J Vis Exp , 2012 , 59 ： 3638 [ 2021－10－08 ]. https://www.jove.com/cn/t/3638/the-mouse-forced-swim-test https://www.jove.com/cn/t/3638/the-mouse-forced-swim-test .

黄璐琦，何春年，马培，等 . 我国药食两用物品产业发展战略思考 [J]. 中国工程科学， 2022 , 24 ( 6 ): 81 － 87 .

罕园园，代解杰 . 抑郁症动物模型与其发病机制研究的进展 [J]. 中国实验动物学报， 2016 , 24 ( 3 ): 321 － 326 .

张中启 . 抗抑郁药与抑郁动物模型 [J]. 军事医学科学院院刊， 2001 ， 25 ( 4 ): 302 － 305 .

AN L , YANG JC , YIN H , et al . Inulin-type oligosaccharides extracted from Yacon produce antidepressant-like effects in behavioral models of depression [J]. Phytother Res , 2016 , 30 ( 12 )： 1937 － 1942 .

RAMAKER MJ , DULAWA SC . Identifying fast-onset antidepressants using rodent models [J]. Mol Psychiatry , 2017 , 22 ( 5 )： 656 － 665 .

KELLY JP , WRYNN AS , LEONARD BE . The olfactory bulbectomized rat as a model of depression: An update [J]. Pharmacol Ther , 1997 , 74 ( 3 )： 299 － 316 .

ALMEIDA RF , GANZELLA M , MACHADO DG , et al . Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances [J]. Prog Neuropsychopharmacol Biol Psychiatry , 2017 , 76 ： 1 － 11 .

HELLWEG R , ZUEGER M , FINK K , et al . Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas [J]. Neurobiol Dis , 2007 , 25 ( 1 )： 1 － 7 .

王婷婷，黄菲，吴辉，等 . 双侧嗅球切除对小鼠行为、海马神经递质及抑郁相关基因表达的影响 [J]. 中国药理学通报， 2015 , 31 ( 5 ): 686 － 691 .

MORALES-MEDINA JC , IANNITTI T , FREEMAN A , et al . The olfactory bulbectomized rat as a model of depression: The hippocampal pathway [J]. Behav Brain Res , 2017 , 317 ： 562 － 575 .

HENDRIKSEN H , MECHIEL KORTE S , OLIVIER B , et al . The olfactory bulbectomy model in mice and rat: One story or two tails [J]. Eur J Pharmacol , 2015 , 753 ： 105 － 113 .

VAVA ， AKOVA MĎURACKOVA Z , TREBATICKA J . Markers of oxidative stress and neuroprogression in depression disorder [J/OL]. Oxid Med Cell Longev , 2015 , 2015 ： 898393 [ 2022－04－17 ]. https://www.hindawi.com/journals/omcl/2015/898393/ https://www.hindawi.com/journals/omcl/2015/898393/ .

BHATT S , NAGAPPA AN , PATIL CR . Role of oxidative stress in depression [J]. Drug Discov Today , 2020 , 25 ( 7 )： 1270 － 1276 .

BILICI M , EFE H , KÖROGLU MA , et al . Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments [J]. J Affect Disord , 2001 , 64 ( 1 )： 43 － 51 .

ENGEL DF , OLIVEIRA J , LIEBERKNECHT V , et al . Duloxetine Protects Human Neuroblastoma Cells from Oxidative Stress-Induced Cell Death Through Akt/Nrf-2/HO-1 Pathway [J]. Neurochem Res ， 2018 , 43 ( 2 ): 387 － 396 .

AKPINAR A , UǦUZ A C , NAZIROǦLU M . Agomelatine and duloxetine synergistically modulates apoptotic pathway by inhibiting oxidative stress triggered intracellular calcium entry in neuronal PC12 cells: role of TRPM2 and voltage-gated calcium channels [J]. J Membr Biol , 2014 , 247 ( 5 ): 451 － 459 .

DEMIRDAŞ A , NAZIROǦLU M ， ÖVEYIS . Duloxetine Reduces Oxidative Stress, Apoptosis, and Ca 2＋ Entry Through Modulation of TRPM2 and TRPV1 Channels in the Hippocampus and Dorsal Root Ganglion of Rats [J]. Mol Neurobiol , 2017 , 54 ( 6 ): 4683 － 4695 .

MEEJURU GF , SOMAVARAPU A , DANDUGA RCSR , et al . Protective effects of duloxetine against chronic immobilisation stress-induced anxiety, depression, cognitive impairment and neurodegeneration in mice [J]. J Pharm Pharmacol , 2021 , 73 ( 4 ): 522 － 534 .

谢守付，马慧，刘伟，等 . 抑郁症模型鼠海马神经元细胞凋亡的初步研究 [J]. 中国神经精神疾病杂志， 2004 ， 30 ( 5 ): 342 － 345 .

袁怀瑞，周颖，崔璐，等 . Visfatin对免疫应激大鼠小肠黏膜细胞凋亡的影响 [C]// 中国畜牧兽医学会动物解剖及组织胚胎学分会第十八次学术研讨会论文集．北京：中国畜牧兽医学会动物解剖及组织胚胎学分会， 2014 : 111 － 120 .

郭敏芳，张慧宇，于婧文，等 . 法舒地尔通过抑制NogoA/NgR信号通路减轻H 2 O 2 诱导的SH-SY5Y人神经母细胞瘤细胞凋亡并增强突触可塑性 [J]. 细胞与分子免疫学杂志， 2022 , 38 ( 7 ): 625 － 631 .

YU HY , YIN ZJ , YANG SJ , et al . Baicalin reverses depressive-like behaviours and regulates apoptotic signalling induced by olfactory bulbectomy [J]. Phytother Res , 2016 , 30 ( 3 )： 469 － 475 .

浏览量

122

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

三七总皂苷抑制JNK/c-Jun信号通路干预钙化性主动脉瓣疾病的效应及机制研究

化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征小鼠颌下腺细胞凋亡和功能的影响

补肾调经方对体外培养氧化应激模型小鼠卵母细胞质量及抗氧化能力的影响

基于HPLC-MS/MS和网络药理学探讨冠心Ⅱ号方治疗急性心肌梗死的作用机制

线叶金雀花对小鼠脑缺血再灌注损伤的保护作用