4周高强度间歇训练调控CUMS大鼠骨骼肌UPRmt改善抑郁样行为  

4-week high-intensity interval training regulates the mitochondrial unfolded protein response in skeletal muscle to improve depressive-like behavior in chronic unpredictable mild stress model rats

作　　者：梁家任 韩雨梅[1] 包春辉 张子威 田俊生[2] 杨永红 向欢[1] LIANG Jiaren;HAN Yumei;BAO Chunhui;ZHANG Ziwei;TIAN Junsheng;YANG Yonghong;XIANG Huan(School of Physical Education,Shanxi University,Taiyuan 030006;China.2.Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006;.3.Shanxi Provincial Institute of Sports Science,Taiyuan 030006;.4.College of Sports Science and Technology,Guangzhou College of Applied Science and Technology,Zhaoqing 526072;.5.Urban and Rural Cultural Development Research Center,Guangzhou College of Applied Science and Technology,Zhaoqing 526072)

机构地区：[1]山西大学体育学院,太原030006 [2]山西大学中医药研究中心,太原030006 [3]山西省体育科学所,太原030006 [4]广州应用科技学院体育科技学院,广东肇庆526072 [5]广州应用科技学院城乡文化发展研究中心,广东肇庆526072

出　　处：《中国比较医学杂志》2025年第3期1-14,共14页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(82374153);山西省基础研究计划项目(202103021224027)。

摘　　要：目的探讨4周高强度间歇训练(high-intensity interval training,HIIT)调控骨骼肌线粒体未折叠蛋白反应(mitochondrial unfold protein reaction,UPRmt)改善慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)大鼠抑郁样行为的作用机制。方法6~8周龄雄性SPF级SD大鼠随机分为对照(C)、模型(M)、HIIT+对照(HC)和HIIT+模型(HM)组。模型组与HIIT+模型组接受8周CUMS建立抑郁模型,HIIT+对照组与HIIT+模型组进行为期4周、每周5 d的HIIT干预,运动方案采用3 min高速(85%~90%Smax)结合1 min低速(50%~55%Smax)无间歇重复训练(规定Smax为最大训练速度)。第4周和第8周评价大鼠的行为学变化,末次行为学测试24 h后进行组织取材,透射电镜检测大鼠骨骼肌线粒体超微结构,ELISA测定三磷酸腺苷(adenosine triphosphate,ATP)和活性氧(reactive oxygen species,ROS)含量,Western blot检测激活转录因子4(activating transcription factor 4,ATF4)、激活转录因子5(activating transcription factor 5,ATF5)、C/EBP同源蛋白(C/EBP-homologous protein,CHOP)和热休克蛋白60(heat shock protein 60,HSP60)蛋白表达水平。结果(1)与对照组比较,模型组大鼠的体质量、穿越格数、直立次数、糖水偏爱率、ATP含量均显著下降(P<0.01),受损线粒体数量、ROS含量、ATF4、ATF5、CHOP、HSP60蛋白表达均显著增加(P<0.01);(2)4周HIIT干预后,与对照组比较,HIIT+对照组大鼠ATP含量、ATF4、ATF5蛋白表达均显著增加(P<0.05,P<0.01),CHOP和HSP60蛋白表达均显著下降(P<0.01);与模型组比较,HIIT+模型组大鼠穿越格数、直立次数、糖水偏爱率、ATP含量、ATF4蛋白表达均显著增加(P<0.01),受损线粒体数量、ROS含量、ATF5、CHOP、HSP60蛋白表达均显著下降(P<0.01);(3)经4周HIIT干预后,CUMS大鼠穿越格数与ATF4蛋白表达、ROS含量与CHOP蛋白表达、受损线粒体数量和ATF5蛋白表达均呈正相关,具有统计学意义(|r|>0.75,P<0.01;|r|>0.75,P<0.05);直立次数与ATF5和HSP60蛋白Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT) regulates the mitochondrial unfolded protein response(UPRmt) in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS). Methods Male SPF-grade SD rats(6~8 weeks old) were divided randomly into control(C), model(M), HIIT+control(HC), and HIIT+model(HM) groups. Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model, while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks. The exercise regimen consisted of 3 min high-speed(85%~90% Smax) combined with 1 min low-speed(50%~55% Smax) uninterrupted repetitive training(Smax is maximum training speed). Behavioral changes were evaluated at weeks 4 and 8. Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy. The ATP and reactive oxygen species(ROS) contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF) 4, ATF5, C/EBP homologous protein(CHOP), and heat shock protein 60(HSP60) were detected by Western blot. Results(1)The body mass, number of crossing grids, number of upright positions, sugar-water preference rate, and ATP content were significantly decreased in group M compared with group C(P<0.01), while the number of damaged mitochondria, ROS content, ATF4, ATF5, CHOP, and HSP60 protein expression were significantly increased(P<0.01).(2)After 4-weeks of HIIT intervention, the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P<0.05, P<0.01). The number of crossing grids, number of upright positions, sugar-water preference rate, ATP content, and ATF4 protein expression were significantly increased in the HM group compared with M group(P<0.01), while the number of damaged mitochondria, ROS content, and ATF5, CHOP, and HSP60 protein exp

关 键 词：HIIT 线粒体功能 UPRmt 抑郁症 骨骼肌 

分 类 号：R-33[医药卫生]