基于Wnt/β-catenin信号转导通路的电针抗抑郁中枢效应机制研究
|
摘要
目的:基于Wnt/β-catenin信号转导通路探究电针抗抑郁中枢效应机制。方法:运用随机数字表法将144只SD大鼠分为空白、模型、电针及西药组,每组又分别依据干预时间进一步分为7d、14d、21d 3个亚组。空白组不接受任何刺激。模型组大鼠采取禁食等方式构建CUMS抑郁大鼠模型。电针组选取百会、神庭穴施以电针。西药组每日灌胃给予氟西汀。分别于第1d、7d、14d、21d观测大鼠行为学指标改变情况。采用蛋白免疫印迹法检测大鼠海马内Wnt/β-catenin信号转导通路中关键蛋白表达。结果:模型组大鼠OFT、SPT评分均较空白组有所下降,体质量减轻,电针组和西药组OFT、SPT评分及体质量检测则较模型组明显上升(P<0.05)。模型组各亚组大鼠wnt1及β-catenin蛋白表达水平下降,GSK-3β蛋白表达水平有所上升,与模型组相比,电针及西药组大鼠Wnt/β-catenin通路中蛋白含量趋近正常水平,且两组与模型组组间比较差异具有统计学意义(P<0.05)。结论:电针可通过调控海马内Wnt/β-catenin信号转导通路中关键蛋白的表达,减轻抑郁症状。
Objective: Probe into the central effect mechanism of electroacupuncture on anti-depression based on Wnt/esf-catenin signal transduction pathway. Methods: 144 SD rats were divided into blank group, model group, electroacupuncture group and western medicine group by random number table method. The blank group did not receive any stimulation. The model group was established by fasting and other methods. The electroacupuncture group selects baihui and shenting cave to perform electroacupuncture. In the western medicine group, fluoxetine was administered daily by gavage. Changes in behavioral indicators were observed on 1 d, 7 d, 14 d and 21 d,respectively. The key protein expressions in the Wnt/hygro-catenin signal transduction pathway in the hippocampus of rats were detected by using protein western blotting. Results: The OFT, SPT scores and body weight of model group were obviously lower than those of the control group, while the OFT, SPT scores and body weight of the electroacupuncture group and the western medicine group were significantly higher than those of the model group(P<0.05). The expression levels of wnt1 and hygrin-catenin in rats in each subgroup were decreased, and the expression levels of gsk-3 human protein were increased. Compared with the model group, the protein levels in Wnt and hygr-catenin pathways in rats in the electroacupuncture and western medicine group were close to normal, and the comparison between the two groups and the model group was statistically significant(P<0.05). Conclusion: Electroacupuncture can reduce depressive symptoms by regulating the expression of key proteins in the Wnt/human-catenin signal transduction pathway in the hippocampus.
Objective: Probe into the central effect mechanism of electroacupuncture on anti-depression based on Wnt/esf-catenin signal transduction pathway. Methods: 144 SD rats were divided into blank group, model group, electroacupuncture group and western medicine group by random number table method. The blank group did not receive any stimulation. The model group was established by fasting and other methods. The electroacupuncture group selects baihui and shenting cave to perform electroacupuncture. In the western medicine group, fluoxetine was administered daily by gavage. Changes in behavioral indicators were observed on 1 d, 7 d, 14 d and 21 d,respectively. The key protein expressions in the Wnt/hygro-catenin signal transduction pathway in the hippocampus of rats were detected by using protein western blotting. Results: The OFT, SPT scores and body weight of model group were obviously lower than those of the control group, while the OFT, SPT scores and body weight of the electroacupuncture group and the western medicine group were significantly higher than those of the model group(P<0.05). The expression levels of wnt1 and hygrin-catenin in rats in each subgroup were decreased, and the expression levels of gsk-3 human protein were increased. Compared with the model group, the protein levels in Wnt and hygr-catenin pathways in rats in the electroacupuncture and western medicine group were close to normal, and the comparison between the two groups and the model group was statistically significant(P<0.05). Conclusion: Electroacupuncture can reduce depressive symptoms by regulating the expression of key proteins in the Wnt/human-catenin signal transduction pathway in the hippocampus.
引文
[1]张迪,王珑,田旭升,等.电针对抑郁大鼠海马组织炎性细胞因子的影响[J].中华中医药学刊, 2017, 35(8):1953-1956
[2]王珑,张迪,田旭升,等.电针对慢性应激抑郁大鼠海马CA3区突触可塑性的影响[J].中国针灸, 2017, 37(2):162-168
[3] Bakhtiarzadeh F, Nahavandi A, Goudarzi M, et al. Axonal transport proteins and depressive like behavior, following Chronic Unpredictable Mild Stress in male rat[J]. Physiology&behavior,2018, 194(2018):9-14
[4] Post R J, Warden M R. Melancholy, anhedonia, apathy:the search for separable behaviors and neural circuits in depression[J]. Current opinion in neurobiology, 2018, 49(2018):192-200
[5] Zwamborn R A J, Snijders C, An N, et al. Wnt Signaling in the Hippocampus in Relation to Neurogenesis, Neuroplasticity, Stress and Epigenetics[J]. Progress in Molecular Biology and Translational Science, 2018[Epub ahead of print]
[6] Kim H, Won S, Hwang D Y, et al. Downregulation of Wnt/β-catenin signaling causes degeneration of hippocampal neurons in vivo[J].Neurobiology of aging, 2011, 32(12):2316. e1-2316. e15
[7] Xia J, Lu Z, Feng S, et al. Different effects of immune stimulation on chronic unpredictable mild stress-induced anxiety-and depression-like behaviors depending on timing of stimulation[J]. International immunopharmacology, 2018, 58(2018):48-56
[8] Liu W, Xue X, Xia J, et al. Swimming exercise reverses CUMSinduced changes in depression-like behaviors and hippocampal plasticity-related proteins[J]. Journal of affective disorders, 2017, 227(2017):126-135
[9] Sato S, Sassone-Corsi P. Circadian and epigenetic control of depression-like behaviors[J]. Current Opinion in Behavioral Sciences,2019, 25(2019):15-22
[10] Zhou Y, Ma C, Li B M, et al. Polygala japonica Houtt. reverses depression-like behavior and restores reduced hippocampal neurogenesis in chronic stress mice[J]. Biomedicine&Pharmacotherapy, 2018, 99(2018):986-996
[11] Reid B S, Yang H, Melvin V S, et al. Ectodermal Wnt/β-catenin signaling shapes the mouse face[J]. Developmental biology, 2011,349(2):261-269
[12]李国栋,姚碧辉,金文海,等.Wnt/β-catenin的表达与肿瘤关系研究进展[J].世界最新医学信息文摘, 2018, 18(07):30-31
[13]曹燕明,王斌,金晶,等.Wnt/β-catenin、RANKL/LGR4通路因子在骨质疏松性骨折端的表达[J].中国骨质疏松杂志, 2018, 24(03):319-323+335
[14] Sequeira A, Klempan T, Canetti L, et al. Patterns of gene expression in the limbic system of suicides with and without major depression[J].Molecular psychiatry, 2007, 12(7):1-16
[15] Wang T L, Ouyang C S, Lin L Z.β-Asarone suppresses Wnt/β-catenin signaling to reduce viability, inhibit migration/invasion/adhesion and induce mitochondria-related apoptosis in lung cancer cells[J]. Biomedicine&Pharmacotherapy, 2018, 106(2018):821-830
[16] Oliva C A, Montecinos-Oliva C, Inestrosa N C. Wnt Signaling in the Central Nervous System:New Insights in Health and Disease[M]//Progress in molecular biology and translational science. Academic Press, 2018, 153(2018):81-130(下转第1043页)
[17] Han X, Wu H, Yin P, et al. Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression[J]. Brain research bulletin, 2018, 139(2018):256-262
[18] Zhang Y, Yuan S, Pu J, et al. Integrated Metabolomics and Proteomics Analysis of Hippocampus in a Rat Model of Depression[J]. Neuroscience, 2018, 371(2018):207-220
[19] Peng W F, Fan F, Li X, et al. Different behavioral and pathological changes between epilepsy-associated depression and primary depression models[J]. Epilepsy&Behavior, 2018, 83(2018):212-218
[20] Tian J, Liu S, He X, et al. Metabolomics studies on corticosteroneinduced PC12 cells:A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism[J].Neurotoxicology and teratology, 2018, 69(2018):27-38
[2]王珑,张迪,田旭升,等.电针对慢性应激抑郁大鼠海马CA3区突触可塑性的影响[J].中国针灸, 2017, 37(2):162-168
[3] Bakhtiarzadeh F, Nahavandi A, Goudarzi M, et al. Axonal transport proteins and depressive like behavior, following Chronic Unpredictable Mild Stress in male rat[J]. Physiology&behavior,2018, 194(2018):9-14
[4] Post R J, Warden M R. Melancholy, anhedonia, apathy:the search for separable behaviors and neural circuits in depression[J]. Current opinion in neurobiology, 2018, 49(2018):192-200
[5] Zwamborn R A J, Snijders C, An N, et al. Wnt Signaling in the Hippocampus in Relation to Neurogenesis, Neuroplasticity, Stress and Epigenetics[J]. Progress in Molecular Biology and Translational Science, 2018[Epub ahead of print]
[6] Kim H, Won S, Hwang D Y, et al. Downregulation of Wnt/β-catenin signaling causes degeneration of hippocampal neurons in vivo[J].Neurobiology of aging, 2011, 32(12):2316. e1-2316. e15
[7] Xia J, Lu Z, Feng S, et al. Different effects of immune stimulation on chronic unpredictable mild stress-induced anxiety-and depression-like behaviors depending on timing of stimulation[J]. International immunopharmacology, 2018, 58(2018):48-56
[8] Liu W, Xue X, Xia J, et al. Swimming exercise reverses CUMSinduced changes in depression-like behaviors and hippocampal plasticity-related proteins[J]. Journal of affective disorders, 2017, 227(2017):126-135
[9] Sato S, Sassone-Corsi P. Circadian and epigenetic control of depression-like behaviors[J]. Current Opinion in Behavioral Sciences,2019, 25(2019):15-22
[10] Zhou Y, Ma C, Li B M, et al. Polygala japonica Houtt. reverses depression-like behavior and restores reduced hippocampal neurogenesis in chronic stress mice[J]. Biomedicine&Pharmacotherapy, 2018, 99(2018):986-996
[11] Reid B S, Yang H, Melvin V S, et al. Ectodermal Wnt/β-catenin signaling shapes the mouse face[J]. Developmental biology, 2011,349(2):261-269
[12]李国栋,姚碧辉,金文海,等.Wnt/β-catenin的表达与肿瘤关系研究进展[J].世界最新医学信息文摘, 2018, 18(07):30-31
[13]曹燕明,王斌,金晶,等.Wnt/β-catenin、RANKL/LGR4通路因子在骨质疏松性骨折端的表达[J].中国骨质疏松杂志, 2018, 24(03):319-323+335
[14] Sequeira A, Klempan T, Canetti L, et al. Patterns of gene expression in the limbic system of suicides with and without major depression[J].Molecular psychiatry, 2007, 12(7):1-16
[15] Wang T L, Ouyang C S, Lin L Z.β-Asarone suppresses Wnt/β-catenin signaling to reduce viability, inhibit migration/invasion/adhesion and induce mitochondria-related apoptosis in lung cancer cells[J]. Biomedicine&Pharmacotherapy, 2018, 106(2018):821-830
[16] Oliva C A, Montecinos-Oliva C, Inestrosa N C. Wnt Signaling in the Central Nervous System:New Insights in Health and Disease[M]//Progress in molecular biology and translational science. Academic Press, 2018, 153(2018):81-130(下转第1043页)
[17] Han X, Wu H, Yin P, et al. Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression[J]. Brain research bulletin, 2018, 139(2018):256-262
[18] Zhang Y, Yuan S, Pu J, et al. Integrated Metabolomics and Proteomics Analysis of Hippocampus in a Rat Model of Depression[J]. Neuroscience, 2018, 371(2018):207-220
[19] Peng W F, Fan F, Li X, et al. Different behavioral and pathological changes between epilepsy-associated depression and primary depression models[J]. Epilepsy&Behavior, 2018, 83(2018):212-218
[20] Tian J, Liu S, He X, et al. Metabolomics studies on corticosteroneinduced PC12 cells:A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism[J].Neurotoxicology and teratology, 2018, 69(2018):27-38