运动对创伤后应激障碍大鼠单胺类递质和炎症的影响  

The effects of treadmill exercise on monoamine neurotransmitter and inflammation in post-traumatic stress disorder rats

作　　者：张君 薛瑞 张有志 邱俊强[1] 魏宏文 Zhang Jun;Xue Rui;Zhang Youzhi;Qiu Junqiang;Wei Hongwen(Exercise Science School,Beijing Sport University,Beijing 100084;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850;Strength and Controlditioning Training College,Beijing Sport University,Beijing 100084,China)

机构地区：[1]北京体育大学运动人体科学学院,北京100084 [2]军事科学院军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京100850 [3]北京体育大学体能训练学院,北京100084

出　　处：《神经解剖学杂志》2021年第5期502-508,共7页Chinese Journal of Neuroanatomy

基　　金：国家科技重大专项新药创制专项(2017ZX09309020);中央高校基本科研业务费专项资金资助课题(2016RB014)。

摘　　要：目的:通过条件性恐惧模型大鼠来评估跑台运动的抗创伤后应激障碍(PTSD)作用,并探讨运动对PTSD影响的可能分子机制。方法:将50只雄性SD大鼠随机分为对照组(control)、条件恐惧模型组(FC)、消退组(EXT)、消退+运动组(EXT+EX)和消退+舍曲林组(EXT+SER)。通过条件恐惧消退保持测试来测试情境恐惧记忆;通过自发活动测试和高架迷宫测试来测试大鼠焦虑样行为;利用酶联免疫法(ELISA)检测大鼠海马肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平;利用高效液相色谱(HPLC)技术测定大鼠海马和前额叶皮质中单胺类神经递质及其代谢产物水平。结果:FC组大鼠的僵住时间增加(P<0.001),进入开臂次数百分比(P<0.01)和开臂时间百分比(P<0.001)减少,而运动和舍曲林均逆转了这些行为缺陷(P<0.05)。FC大鼠海马中TNF-α水平(P<0.05)和IL-1β水平(P<0.05)显著升高,FC大鼠海马和皮层中的去甲肾上腺素(NE)水平(P<0.05)以及多巴胺(DA)水平(P<0.05)显著升高。而舍曲林给药显著降低了海马中TNF-α水平(P<0.05),跑台运动和舍曲林给药显著均显著降低了海马中IL-1β水平(运动:P<0.05;舍曲林:P<0.01)和5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)水平(P<0.05),同时显著降低了皮层中NE水平(P<0.01)和DA水平(P<0.05)。结论:跑台运动改善了条件恐惧模型大鼠的情境恐惧记忆和焦虑样行为。单胺类神经递质NE和DA以及炎性因子TNF-α和IL-1β可能参与了跑台运动对PTSD的缓解作用。Objective:This study aimed to investigate whether or not treadmill training has therapeutic effects on post-traumatic stress disorder(PTSD)rats by developing fear conditional(FC)model,and to explore the underlying mechanisms on alleviating the PTSD.Methods:Fifty male SD rats were randomly divided into control group(control),FC model group(FC),extinction group(EXT),extinction+exercise group(EXT+EX)and extinction+sertraline treatment group(EXT+SER).Behavioral test controltextual freezing measurement was performed to measure controltextual fear controlditioning,the locotomor activity test and elevated plus-maze test were performed to measure anxietylike behavior.ELISA was used to determine the levels of inflammatory cytokines TNF-αand IL-1β.High-performance liquid chromatography(HPLC)technology was used to determine the levels of monoamine neurotransmitters and their metabolites in the hippocampus and prefrontal cortex.Results:The FC procedures induced an increase in the freezing time(P<0.001)and a decrease in the percentage of entries into the open arms(P<0.01)and time spent in the open arms(P<0.001),and that these behavioral deficiencies were reversed by treadmill exercise and sertraline(P<0.05).FC rats significantly increased TNF-αlevels(P<0.05)and IL-1βlevels(P<0.05)in the hippocampus.FC rats increased norepinephrine(NE)levels(P<0.05)and dopamine(DA)levels(P<0.05)in the hippocampus and the prefrontal cortex.The sertraline significantly decreased TNF-αlevels(P<0.05)in the hippocampus.The treadmill exercise and the sertraline significantly decreased IL-1βlevels(EXT+EX:P<0.05;EXT+SER:P<0.01)and 5-HIAA levels(P<0.05)in the hippocampus.Besides,they also significantly decreased NE levels(P<0.01)and DA levels(P<0.05)in the prefrontal cortex.Conclusion:The present study demonstrated that treadmill exercise ameliorated contextual fear conditioning and anxiety-like behavior in FC model.Mechanism studies indicated that monoamine neurotransmitter NE and DA and inflammatory cytokines TNF-αand IL-1βmay be involved in

关 键 词：创伤后应激障碍 跑台运动 单胺类神经递质 炎性因子 大鼠 

分 类 号：R749.5[医药卫生—神经病学与精神病学]