百事乐胶囊对慢性应激抑郁模型大鼠海马、皮质显微结构的协同保护效应
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摘要
目的:探讨百事乐胶囊对慢性应激抑郁模型大鼠海马、皮质显微结构的保护作用。方法:将SD大鼠随机分为6组,即空白对照、抑郁模型、氟西汀(5.4 mg/kg)、百事乐胶囊高、中、低(2.88、1.44、0.72 g/kg)剂量组,采用慢性不可预见性温和应激的方法建立抑郁模型,于造模同时给药,连续21 d。采用新奇摄食实验、强迫游泳实验观察模型动物的行为学变化,Golgi-Cox染色观察大鼠皮质、海马病理结构的变化。结果:与正常组比较,模型组大鼠摄食潜伏期、强迫游泳不动时间增长(P<0.01),皮质区分子层、外粒层、外锥体层神经元丢失严重,外锥体层、内粒层、内锥体层的神经元排列呈混乱和无序状态;海马CA1、CA3、DG区神经元数目明显减少,核固缩,细胞质萎缩;氟西汀、百事乐胶囊高、中剂量能显著降低模型大鼠的摄食潜伏期、强迫游泳不动时间(P<0.01或P<0.05);氟西汀、百事乐胶囊高剂量可增加皮质区分子层、外粒层、外锥体层及海马CA1区神经元存活的数量,减少细胞核深染和固缩,并能促进外锥体层、内粒层、内锥体层神经元的有序排列、致密;同时氟西汀、百事乐胶囊高剂量可显著减少海马CA3、DG区神经元细胞黑色深染及胞体形态的畸变。结论:百事乐胶囊可通过协同保护海马、皮质的显微结构而实现其抗抑郁的作用。
Objective: To investigate the protective effect of Baishile Capsule on hippocampal and cortical microstructure in chronic depression model rats. Methods: SD rats were randomly divided into six groups: control group,model group,fluoxetine group( 5. 4 mg/kg),high,medium and low dose of Baishile Capsule groups( 3. 84,1. 92,0. 96 g/kg). The chronic unpredictable mild stress was used to establish model of depression,administered simultaneously in modeling,which continued to 21 d. Novel feeding test and forced swiming test were used to detect depression-like behavior in rats,and Golgi-Cox staining was used to observe the pathological changes of cortex and hippocampus. Results:Compared with normal group,the latent period and immobile time were obviously increased in model group( P < 0. 01).The neurons of outer cone layer,inner granule layer and inner pyramid layer were confused and disordered. The numbers of neurons in CA1,CA3 and DG of hippocampus were significantly decreased,nuclear condensation and cytoplasm atrophy. Fluoxetine,high and medium dose of Baishile Capsule could significantly decrease the time of latent period and immobility( P < 0. 01 or P < 0. 05). Fluoxetine and high dose of Baishile Capsule increased the number of neurons in cortical layer,extracellular layer,extrapyramidal layer and hippocampal CA1 area,reduced the nucleus staining and shrinkage,and could promote the orderly arrangement and dense of the outer cone,inner granule,pyramidal neurons. Meanwhile,the situations that deep dyeing of the hippocampal CA3 and DG neurons and morphological distortion of the cell body were reduced after administration of fluoxetine or Baishile Capsule. Conclusion: Baishile Capsule could exert its antidepressant role by synergistically protecting the microstructure of hippocampus and cortex.
Objective: To investigate the protective effect of Baishile Capsule on hippocampal and cortical microstructure in chronic depression model rats. Methods: SD rats were randomly divided into six groups: control group,model group,fluoxetine group( 5. 4 mg/kg),high,medium and low dose of Baishile Capsule groups( 3. 84,1. 92,0. 96 g/kg). The chronic unpredictable mild stress was used to establish model of depression,administered simultaneously in modeling,which continued to 21 d. Novel feeding test and forced swiming test were used to detect depression-like behavior in rats,and Golgi-Cox staining was used to observe the pathological changes of cortex and hippocampus. Results:Compared with normal group,the latent period and immobile time were obviously increased in model group( P < 0. 01).The neurons of outer cone layer,inner granule layer and inner pyramid layer were confused and disordered. The numbers of neurons in CA1,CA3 and DG of hippocampus were significantly decreased,nuclear condensation and cytoplasm atrophy. Fluoxetine,high and medium dose of Baishile Capsule could significantly decrease the time of latent period and immobility( P < 0. 01 or P < 0. 05). Fluoxetine and high dose of Baishile Capsule increased the number of neurons in cortical layer,extracellular layer,extrapyramidal layer and hippocampal CA1 area,reduced the nucleus staining and shrinkage,and could promote the orderly arrangement and dense of the outer cone,inner granule,pyramidal neurons. Meanwhile,the situations that deep dyeing of the hippocampal CA3 and DG neurons and morphological distortion of the cell body were reduced after administration of fluoxetine or Baishile Capsule. Conclusion: Baishile Capsule could exert its antidepressant role by synergistically protecting the microstructure of hippocampus and cortex.
引文
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[14]宋晓灵,张芳,曹莉莎.氟西汀对抑郁大鼠模型海马CA1区、CA3区及齿状回区神经生长因子表达的影响[J].武汉大学学报(医学版),2015,2:185-188.
[15]Qiao H,An SC,Ren W,et al.Pmgressive alterations of hippocampal CA3·CA1 synapses in an animal model of depression[J].Behav Brain Res,2014,275:19l-200.
[16]Sousa N,Lukoyanov NV,Madeira MD,et a1.Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement[J].Neuroscience,2000,97(2):253-266.
[2]Clark DA,Beck AT.Cognitive theory and therapy of anxiety and depression:convergence with neurobiological findings[J].Trends Cogn Sci,2010,14(9):418-424.
[3]Zheng C,Zhang T.Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex pathway in depression[J].Neuroscience,2015,292:170-180.
[4]Gosnell SN,Velasquez KM,Molfese DL,et al.Prefrontal cortex,temporal cortex,and hippocampus volume are affected in suicidal psychiatric patients[J].Psychiatry Res,2016,30(10):50-56.
[5]韩远山,王宇红,孟盼,等.百事乐胶囊对抑郁模型大鼠海马神经元显微结构及凋亡的影响[J].时珍国医国药,2015,26(1):44-47.
[6]张秀丽,孟盼,王宇红,等.百事乐胶囊对慢性应激抑郁模型大鼠海马DG、CA3区神元再生相关蛋白的影响[J].中国中医药信息杂志,2015,22(5):52-56.
[7]赵洪庆,杜青,凌佳,等.左归降糖解郁方对糖尿病并发抑郁症大鼠海马神经元JNK/Elk-1/c-fos通路的调控作用[J].中国临床药理学与治疗学,2016,21(6):625-629.
[8]Brill MS,Kleele T,Ruschkies L,et al.Branch-Specific Microtubule Destabilization Mediates Axon Branch Loss during Neuromuscular Synapse Elimination[J].Neuro,2016,16:30654-30657.
[9]Kurczek J,Wechsler E,Ahuja S,et al.Differential contributions of hippocampus and medial prefrontal cortex to self-projection and self-referential processing[J].Neuropsychologia,2015,73:116-126.
[10]Quan M,Zheng C,Zhang N,et a1.Impairments of behavior,infomation flow between thalamus and cortex,and prefrontal cortical synaptic plasticity in an animal model of depression[J].Brain Res Bull,2011,85:109-116.
[11]舒先涛,陈运才.海马促肾上腺皮质激素释放因子与神经元树突发育[J].解剖学杂志,2008,31(3):433-435.
[12]Winkowski DE,Kanold PO.Laminar transformation of frequency organization in auditory cortex[J].J Neurosci,2013,33(4):1498-1508.
[13]Treccani G,Gaarn du Jardin K,Wegener G,et al.Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression[J].Synapse,2016,70(11):471-474.
[14]宋晓灵,张芳,曹莉莎.氟西汀对抑郁大鼠模型海马CA1区、CA3区及齿状回区神经生长因子表达的影响[J].武汉大学学报(医学版),2015,2:185-188.
[15]Qiao H,An SC,Ren W,et al.Pmgressive alterations of hippocampal CA3·CA1 synapses in an animal model of depression[J].Behav Brain Res,2014,275:19l-200.
[16]Sousa N,Lukoyanov NV,Madeira MD,et a1.Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement[J].Neuroscience,2000,97(2):253-266.