【作者】 张君；

【导师】 魏宏文；

【作者基本信息】 北京体育大学 ， 体育教育训练学， 2019， 硕士

【摘要】 创伤后应激障碍(Post-traumatic Stress Disorder,PTSD)是一种经历威胁性事件所引起的延迟性或持久性的应激性焦虑精神障碍。许多研究发现适度、规律的运动不但可以健体,还可以健脑,有效提高认知功能、改善心理状态、预防脑相关的疾病和心理障碍。本研究从制备创伤后应激障碍模型入手,通过时间依赖性敏化(Time-dependent sensitization,TDS)模型和条件恐惧(Fear conditioning,FC)模型来评估适度跑台运动的抗PTSD作用,探讨在造模早期预防性给予4-5周的跑台运动预防和治疗PTSD发生的可能性,并进一步探讨运动治疗TDS模型大鼠可能的分子机制。本研究首先通过测试大鼠焦虑样行为评价运动抗PTSD效应;利用高效液相色谱(High-performance liquid chromatography,HPLC)技术用于测定TDS大鼠海马和前额叶皮质中单胺类神经递质及其代谢产物的水平、Elisa试剂盒检测海马炎性因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平、蛋白免疫印迹(Western blot)方法用于检测BDNF/PI3K/Akt/CREB蛋白信号通路中的关键蛋白表达。结果:(1)与正常对照CON组相比,TDS组大鼠均出现了焦虑样行为,例如僵住时间的增加(P<0.001)以及进入开臂次数百分比减少(P<0.05),而运动和舍曲林均逆转了这些行为缺陷(P<0.05)。(2)与正常对照CON组相比,FC组和EXT组第6天僵住时间均显著升高(P<0.001),而EXT组与FC组僵住时间无统计学差异,而运动和舍曲林僵住时间均显著降低大鼠僵住时间(P<0.05)。(3)单胺神经递质测定显示,TDS大鼠海马中的5-羟色胺(serotonin,5-HT)水平显著降低(P<0.05),而前额皮质中的多巴胺(dopamine,DA)水平显著升高(P<0.05),跑台运动显著增加了海马中5-HT水平(P<0.05),并降低了前额皮质中DA水平(P<0.05)。(4)Elisa试剂盒检测结果显示,与CON组相比,TDS组大鼠海马TNF-α水平显著增高(P<0.05),而跑台运动显著减少了大鼠海马TNF-α水平(P<0.05)。(5)Western数据表明,与CON组相比,TDS大鼠海马BDNF、TrkB、pAkt、pCkB水平均显著增高(P<0.05、P<0.01),与TDS组相比,运动组大鼠海马中BDNF、TrkB、pAkt、pCREB均显著性降低(P<0.05、P<0.01)。以上结果提示,跑台运动改善了两种大鼠创伤后应激障碍模型中的情境恐惧条件反射和焦虑样行为。可能涉及单胺神经递质例如海马5-HT水平,前额叶皮层DA水平,炎性因子TNF-α水平的改变,以及BDNF和相关PI3K/AKT/CREB信号通路,均可能参与了跑台运动对缓解PTSD的治疗作用。更多还原

【Abstract】 Post-traumatic stress disorder(PTSD)is a disabling anxiety disorder that occurs when someone is exposure to catastrophic and threatening events,such as: natural disasters,wartime situations,traffic accidents and/or terrorist attacks.Research based evidence supports the beneficial effects of regular physical exercise on physical health,cognitive deficits and mood disorders such as anxiety and depression.This study aimed to investigate whether or not treadmill exercise has therapeutic effects in two Post-traumatic stress disorder(PTSD)models,and to explore the underlying mechanisms on one of the PTSD models.A time-dependent sensitization(TDS)model and a fear conditioning(FC)model were developed to evaluate the anti-PTSD-like effects of moderate treadmill exercise with 4/5-week running programm.This study explored the relationship between anti-inflammatory effects of exercise on PTSD rats.High-performance liquid chromatography(HPLC)technology was used to determine the levels of monoamine neurotransmitters in the hippocampus and prefrontal cortex in TDS rats.The western blot method was used to assay key proteins expression in BDNF/PI3K/Akt/CREB signaling pathway.Our results showed that(1)the TDS and FC procedures induced several behavioral deficiencies,such as an increase in the freezing time(P<0.001)and a decrease in the percentage of entries into the open arms and time spent in the open arms(P<0.05),and that these deficiencies were reversed by treadmill exercise(P<0.05).(3)Further monoamine assays revealed that the treadmill exercise significantly increased serotonin(5-HT)levels(P<0.05)in the hippocampus and decreased dopamine(DA)levels(P<0.05)in the prefrontal cortex.(4)Elisa test showed that TDS rat significantly decreased the level of TNF-α(P<0.05)compared with CON.Exercise significantly increased the level of TNF-α(P<0.05).(5)Western blotting data demonstrated that exercise normalized the decreased BDNF/TrkB/pAkt/pCREB levels(P<0.05、P<0.01)in the hippocampus in TDS rats compared with TDS.The present study demonstrated that treadmill exercise ameliorated contextual fear conditioning and anxiety-like behavior in two rat PTSD models.Mechanism studies indicated that increased 5-HT levels in the hippocampus decreased DA levels in the prefrontal cortex and increased TNF-α levels,as well as upregulation of BDNF and the related PI3K/AKT/CREB signaling pathway,may be involved in the therapeutic effects of treadmill exercise on alleviating the PTSD.更多还原