有氧运动激活BDNF/miR-195/Bcl-2信号通路抑制CUMS抑郁小鼠海马神经细胞凋亡  

Aerobic Exercise Activates the Hippocampus BDNF/miR-195/Bcl-2 Signaling Pathway Axis and Inhibits Hippocampus Neuronal Apoptosis in Mice Model with CUMS Depression

作　　者：屈红林[1,2] 谢军[2] 陈嘉勤[1] 刘瑞莲[2] 彭琪[1] 李娣[1] 陈伟[1] 陈伊琳[1] 陈锐[1] 卲长凤 袁阿芳 QU Honglin;XIE Jun;CHEN Jiaqin;LIU Ruilian;PENG Oi;LI Di;CHEN Wei;CHEN Yilin;CHEN Rui;SHAO Changfeng;YUAN Afang(Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province,Hunan Normal University,Changsha 420012,China;Institute of Sport Sciences,Yichun University,Yichun 336000,China)

机构地区：[1]湖南师范大学湖南省体适能与运动康复重点实验室,湖南长沙420012 [2]宜春学院体育科学研究所,江西宜春336000

出　　处：《天津体育学院学报》2018年第2期148-155,176,共9页Journal of Tianjin University of Sport

基　　金：湖南省教育厅科技重点项目(项目编号:2016-1293);江西省卫生计生委科技计划项目(项目编号:20183019);江西省教育厅科学技术研究重点项目(项目编号:GJJ161006).

摘　　要：目的:探讨有氧运动激活慢性不可预知应激性刺激(Chronic Unpredictable Stress,CUMS)抑郁小鼠海马BDNF/miR-195/Bcl-2信号通路改善海马功能的作用。方法:8周龄雄性健康KM小鼠,随机数字法分为空白对照组(CG)、CUMS抑郁模型组(MG)和抑郁+有氧运动组(EG),每组12只。13种慢性不可预知应激刺激28天建立CUMS抑郁模型,EG组在建模成功后适应性运动1周后,采用小动物跑台进行8周的有氧运动训练。训练结束后测定各组小鼠的神经行为评分,ELISA法测定血清BDNF,免疫组化法进行海马组织BDNF的定位表达,TUNEL检测海马组织细胞凋亡率,RTPCR检测凋亡相关miRNA与m RNA的表达水平,western blot检测海马BDNF蛋白表达水平。结果:CUMS抑郁小鼠海马功能显著降低,神经行为学评分下降,血清BDNF含量降低,造模效果显著。mRNA与miRNA高度相关的基因涉及到miR-195与BDNF,且两者的差异表达量与有氧运动相关,RT-PCR检测模型组小鼠海马组织Bax、Caspase-3表达上调,Bcl-2表达下降。有氧运动可有效改善抑郁小鼠海马功能,上调海马组织BDNF与Bcl-2的表达水平,下调miR-195和Bax的表达水平,抑制Caspase-3的活化,降低海马细胞凋亡率,且海马miR-195表达水平与BDNF表达呈显著负相关。结论:CUMS抑郁小鼠海马miR-195上调通过靶向抑制Bcl-2的表达水平促进海马细胞凋亡。有氧运动可显著上调抑郁小鼠海马BDNF的表达水平,抑制miR-195在小鼠海马细胞中的促凋亡作用,下调Bax、Caspase-3的表达,发挥抗凋亡作用。这一作用可能与BDNF/miR-195/Bcl-2信号通路的激活有关。Objective:The purpose of this study was to explore the effect of aerobic exercise on hippocampus BDNF,miR-195/Bcl-2 signaling pathway and hippocampus neuronal apoptosis in mice with chronic unpredictable stress depression.Methods:Thirty-six male 8-week old Kunming mice were included in this study,12 of them were in control group(CG),24 were established depression model by CUMS which was used 13 chronic unpredictable stress stimuli for 28days,and then were divided into model group(MG)and model plus exercise group(EG)(n=12).0ne week after adaptive training,EG group mice performed 8 weeks of aerobic training(Training program:10m/min,0 slope,60 min/d and 6 times/week.)with a small animal treadmill.Nenroethological assessments were implemented on the last day of training.The samples were collected after anesthesia the next day.The level of serum BDNF was assessed by ELISA,TUNEL was used to detect the apoptosis rate,the expression level of hippocampus BDNF,Bcl-2,Bax?Caspase-3 and miR-195 were examined by RT-PCR,the expression of hippocampus BDNF were detected by immunohistochemistry,and the expression of hippocampus BDNF was tested by Western blot.Results:The CUMS depression raice,function was significantly impaired,the nenrobehavioral score was decreased,the expression of serum BDNG was decreased.Aerobic exercise improved the hippocampus function of depressed mice,decreased Bax,Gaspase-3,increased the level of BDNF,up-regulated the expression of BDNF and Bcl-2,reduced hippocampus cell apoptosis and the expression of miR-195 and Bax,inhibited the expression of Caspase-3.miR-195 expression was negatively correlated to the expression of BDNF.Conclusions:The up-regulation of miR-195 in the hippocampus of CUMS depression mice promotes apoptosis of hippocam-pus cells through targeting inhibition of Bcl-2.Aerobic exercise can significantly increase the expression of BDNF in the hippocampus of depression mice inhibit the pro-apoptotic effect of miR-195 in mice hippocampus cells,reduce the expression of Bax,Caspase-3 and inhib

关 键 词：有氧运动 BNDF/miR-195/Bcl-2信号通路 CUMS抑郁症 海马 凋亡 

分 类 号：G804.2[文化科学—运动人体科学]