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。
关键词： 运动；慢性应激抑郁模型；神经营养
中图分类号： G804.5文献标识码： A文章编 号： 1007-3612(2011)05-0043-05
Effect of Exercise on Neurotrophic Signal Pathway in ChronicaleUnpredictablly Stressed Rats
WEI Hongwen1, JIAO Wei1, ZHANG Youzhi2, ZHANG Liming 2, CHEN Hongxia2, XUE Rui2
(1.Beijing SportUniversity，Beijing 100084，China;2Institute of Pharmacology and Toxicology，Academy of Military Medical Science，B eijing 100850，China)
Abstract:Objective: To investigate the effect of exercise on neurotrophic signal pathwayin the chronically unpredictable stress (CUS) animal model of depression, and di scuss partial antidepressant mechanism of exercise.Methods: 56 male SD rats wer e divided into seven groups: Control, CUS, Fluoxetine (Flu), low intensity tread mill running (LIR), moderate intensity treadmill running (MIR), Flu+LIR and Flu+ MIR.After four weeks of CU S, hippocampal brain-derived neurotrophic factor (BDNF), extracellular signal re gulated kinase (ERK1/2) and phosphor-extracellular signal regulated kinase(pERK 1/2), and neuropeptide VGF expression were tested using western-blotResults:1) CUS down-regulated significantly the expression of pERK, BDNF and VGF in hip pocampusFlu, MIR, Flu+LIR and Flu+MIR could improve these changes obviouslyFlu+LIR up-reguated the expression of hippocampal pERK and BDNF but did notaffect the expression of hippocampal VGF markedly.2) The up-regulaed effect o f MIR and Flu+LIR on the expression of hippocampal pERK was better than that ofLIRThe up-regulated effect of Flu+MIR on the expression of hippocampal BDNF w as better than that of Flu or MIR respectively; Flu+LIR was better than LIR.Co nclusions: 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 rel ated to BDNF’s signal pathway may be underlying the neurotrophic and neuroplast ic effects of exercise;2) The neurotrophic effect of fluoxetine can be enhance d further by exercise
Key words:depression; exercise; neurotrophy
目前研究认为，抑郁症的发生不仅与脑内神经递质及其受体有关，还涉及受体后信号传 导系统及基因转录过程，从而引起特定脑区神经营养障碍，神经可塑性下降等改变［1 ］。神经营养因子及其信号传导通路可能参与并介导了抗抑郁剂的作用［2］。
适量运动可以通过保护神经元［3］、促进神经再生［4］和增加海马脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)的表达［5 ］来促进脑可塑性。本课 题组前期对大鼠慢性应激抑郁模型施加运动干预，行为学评价结果显示运动对慢性应激抑 郁模型具有抗抑郁样作用［6］。本实验旨在前期研究的基础上，从神经营养通路重 要分子表达水平出发，探讨运动抗抑郁作用可能存在的机制。