运动对慢性应激抑郁模型大鼠海马BDNF通路的影响  

Effect of Exercise on Neurotrophic Signal Pathway in Chronicale Unpredictablly Stressed Rats

作　　者：魏宏文[1] 矫玮[1] 张有志[2] 张黎明[2] 陈红霞[2] 薛瑞[2] 

机构地区：[1]北京体育大学,北京100084 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《北京体育大学学报》2011年第5期43-47,共5页Journal of Beijing Sport University

基　　金：北京体育大学博士学位论文(部分)

摘　　要：目的:观察运动对慢性应激抑郁模型大鼠海马神经营养通路的影响,探讨其抗抑郁作用可能的部分机理。方法:56只雄性大鼠随机分为7组:Control组、CUS组、氟西汀组(Flu)、小强度跑台训练(LIR)、中等强度跑台训练(MIR)、Flu+LIR、Flu+MIR。应用免疫组织化学法和western-blotting法,检测运动和氟西汀对CUS大鼠海马神经元形态、结构、数目,海马神经细胞微管相关蛋白-2C(MAP-2C)及神经营养通路重要信号分子细胞外信号调节激酶(ERK)、磷酸化ERK(pERK)、脑源性神经营养因子(BDNF)、VGF神经肽蛋白表达的影响。结果:1)CUS显著下调海马pERK、BDNF和VGF的表达,Flu、MIR、Flu+MIR和Flu+LIR,均能够显著改善这种情况。Flu+LIR显著上调CUS大鼠海马pERK和BDNF的表达,未能明显上调VGF的表达;2)对CUS大鼠海马pERK表达的上调,MIR、Flu+LIR显著优于LIR。对CUS大鼠BDNF表达的上调,Flu+MIR显著优于Flu或者MIR的单独干预;Flu+LIR显著优于LIR的单独干预。结论:1)运动可以上调慢性应激大鼠海马BDNF及其相关的神经营养通路重要信号分子pERK和VGF的表达。这有利于保护应激状态下海马结构和功能的进一步被破坏,促进神经营养和神经可塑性。2)运动能够增强氟西汀的神经营养作用。Objective： To investigate the effect of exercise on neurotrophic signal pathway in the chronically unpredictable stress（CUS） animal model of depression,and discuss partial antidepressant mechanism of exercise.Methods： 56 male SD rats were divided into seven groups： Control,CUS,Fluoxetine（Flu）,low intensity treadmill running（LIR）,moderate intensity treadmill running（MIR）,Flu＋LIR and Flu＋MIR.After four weeks of CUS,hippocampal brain-derived neurotrophic factor（BDNF）,extracellular signal regulated kinase（ERK1/2） and phosphor-extracellular signal regulated kinase（pERK1/2）,and neuropeptide VGF expression were tested using western-blot.Results： 1） CUS down-regulated significantly the expression of pERK,BDNF and VGF in hippocampus.Flu,MIR,Flu＋LIR and Flu＋MIR could improve these changes obviously .Flu＋LIR up-reguated the expression of hippocampal pERK and BDNF but did not affect the expression of hippocampal VGF markedly.2） The up-regulaed effect of MIR and Flu＋LIR on the expression of hippocampal pERK was better than that of LIR.The up-regulated effect of Flu＋MIR on the expression of hippocampal BDNF was better than that of Flu or MIR respectively;Flu＋LIR was better than LIR.Conclusions： The antidepressant mechanisms of exercise may be related to following： exercise can antagonize the chronic stress-induced hipocampal impairment via： 1） up-regalting the expression of hippocampal BDNF,pERK and VGF which were related to BDNF＇s signal pathway may be underlying the neurotrophic and neuroplastic effects of exercise;2） The neurotrophic effect of fluoxetine can be enhanced further by exercise.

关 键 词：运动 慢性应激抑郁模型 神经营养 

分 类 号：R87[医药卫生—运动医学]