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引用本文:屈红林,谢 军,陈嘉勤,刘瑞莲,彭 琪,李 娣,陈 伟,陈伊琳,陈 锐,卲长凤,袁阿芳.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[J].天津体育学院学报,2018,33(2):148-155
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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
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1, 袁阿芳1
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
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 mRNA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。
关键词:  有氧运动  BNDF/miR-195/Bcl-2信号通路  CUMS抑郁症  海马  凋亡
DOI:10.13297/j.cnki.issn1005-0000.2018.02.008
分类号:
基金项目: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)
Aerobic Exercise Activates the Hippocampus BDNF/miR-195/Bcl-2 Signaling Pathway Axis and Inhibits Hippocampus Neuronal Apoptosis in Mice Model with CUMS Depression
QU Honglin1,2, XIE Jun2, CHEN Jiaqin1, LIU Ruilian2, PENG Qi1, LI Di1, CHEN Wei1, CHEN Yilin1, CHEN Rui1, SHAO Changfeng1, YUAN Afang1
1.Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province,Hunan Normal University,Changsha 420012,China;2.Institute of Sport Sciences,Yichun University,Yichun 336000,China
Abstract:
Objective:The purpose of this study was to explore the effect of aerobic exercise on hippocampus BDNF,miR-195/Bcl-2 signaling pathway and hip? pocampus 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).One 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. Neuroethological 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 de? pression mice’function was significantly impaired,the neurobehavioral score was decreased,the expression of serum BDNG was decreased. Aerobic exercise improved the hippocampus function of depressed mice,decreased Bax,Caspase-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 cor? related to the expression of BDNF. Conclusions:The up-regulation of miR-195 in the hippocampus of CUMS depression mice promotes apoptosis of hippocampus cells through targeting inhibition of Bcl-2.Aerobic exercise can significantly increase the expression of BDNF in the hippocampus of depression mice,inhib? it the pro-apoptotic effect of miR-195 in mice hippocampus cells,reduce the expression of Bax,Caspase-3 and inhibit apoptosis of hippocampus,improve hip? pocampus function. The protective effect of aerobic exercise on hippocampus function in CUMS depression mice was related to the activation of the BDNF/miR- 195/Bcl-2 signaling pathway.
Key words:  aerobic exercise  BDNF/miR-195/Bcl-2 signaling pathway  CUMS depression  hippocampus  apoptosis
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