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基于Wnt/β-catenin与Notch信号通路探讨电针对抑郁大鼠海马神经元再生的作用机制

冉立成 尚辉 袁艺 陈丽荣 杨通 李磊 王亚军

针刺研究2024,Vol.49Issue(12):1282-1288,7.
针刺研究2024,Vol.49Issue(12):1282-1288,7.DOI:10.13702/j.1000-0607.20230664

基于Wnt/β-catenin与Notch信号通路探讨电针对抑郁大鼠海马神经元再生的作用机制

Mechanism of electroacupuncture on hippocampal neuron regeneration in depression rats based on Wnt/β-catenin and Notch signaling pathway

冉立成 1尚辉 1袁艺 1陈丽荣 1杨通 1李磊 1王亚军1

作者信息

  • 1. 甘肃中医药大学针灸推拿学院,兰州 730000
  • 折叠

摘要

Abstract

Objective To observe the effect of electroacupuncture(EA)on the proliferation of hippocampal neurons and Wnt/β-catenin and Notch signaling pathways in depression like behavior rats,so as to explore its mechanism underlying improvement of depression.Methods SD rats were randomly divided into blank,model,medication and EA groups,with 12 rats in each group.The depression model was established by chronic unpredictable mild stimulation combined with solitary raising for 35 consecutive days.After 14 days modeling,EA was applied to"Baihui"(GV20)and"Taichong"(LR3)for 15 min once daily for 3 weeks.For rats of the medication group,clomipramine(2.5 mg/kg)was given(i.p.)once a day for 3 weeks.The depression-like behavior was evaluated by open field test and forced swimming test.The ultrastructure of hippocampal neurons was observed by transmission electron microscope(TEM).The positive expression of 5-bromo-2'-deoxyuridine/neuron-specific nucleoprotein(BrdU/NeuN)in hippocampal dentate gyrus of rats was detected by immunofluorescence double labeling method.Western blot was used to detect the relative expression of Wnt/β-catenin and Notch pathway key proteins β-catenin,G1/S-specific cyclin-D1(Cyclin D1),NICD and Hes1 in hippocampus of rats.Results Compared with the blank group,the total distance and average speed of open field movement were decreased(P<0.01),and the immobility time of forced swimming was increased(P<0.01).The positive expression of BrdU/NeuN in hippocampal dentate gyrus was decreased(P<0.01).The relative expression of β-catenin and Cyclin D1 protein in hippocampus were decreased(P<0.01),while the relative expression of NICD and Hes1 protein increased(P<0.01)in the model group.Following the treatment and compared with the model group,the total distance and average speed of movement in the open field were increased(P<0.05),and the immobility time of forced swimming was decreased(P<0.05)in both medication and EA groups.The positive expression of BrdU/NeuN in hippocampal dentate gyrus was increased(P<0.01).The relative expression of β-catenin and Cyclin D1 protein in hippocampus were increased(P<0.01),while the relative expression of NICD and Hes1 protein were decreased(P<0.01,P<0.05)in both medication and EA groups.TEM microscope observation showed irregularity of hippocampal neurons,rupture of nuclear membranes,disruption of mitochondrial structure,and dilation of endoplasmic reticulum in the model group,which was relatively milder in both medication and EA groups.Conclusion EA can improve the depressive state of depression model rats,which may be associated with its functions in regulating Wnt and Notch signaling pathways,thereby promoting the regeneration of hippocampal neurons.

关键词

抑郁症/电针/神经元再生/Wnt/Notch

Key words

Depression/Electroacupuncture/Neuronal regeneration/Wnt/Notch

引用本文复制引用

冉立成,尚辉,袁艺,陈丽荣,杨通,李磊,王亚军..基于Wnt/β-catenin与Notch信号通路探讨电针对抑郁大鼠海马神经元再生的作用机制[J].针刺研究,2024,49(12):1282-1288,7.

基金项目

国家自然科学基金项目(No.82160936) (No.82160936)

针刺研究

OA北大核心CSTPCDMEDLINE

1000-0607

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