PGC-1α启动子甲基化介导在热大鼠预适应延缓运动疲劳中的机制研究  

Study on the mechanism of PGC-1αpromoter methylation mediated by thermal pre adaptation in delaying exercise fatigue

作　　者：赵海涛 曹庆雷 邓中原 ZHAO Haitao;CAO Qinglei;DENG Zhongyuan(Dept.of Physical Education,University of Science and Technology Beijing,100083)

机构地区：[1]北京科技大学体育部,北京100083 [2]郑州大学农学院

出　　处：《中国康复医学杂志》2022年第10期1306-1311,共6页Chinese Journal of Rehabilitation Medicine

摘　　要：目的:探讨热预适应通过调节过氧化物酶体增殖物活化受体γ协同刺激因子-1α(peroxisome proliferator-activated receptor-γcoactivator-1α,PGC-1α)基因的启动子甲基化修饰从而延缓运动疲劳发生的机制。方法:选取12只8周龄雄性SD大鼠随机分成热预适应组(n=6)与正常对照组(n=6),热预适应组经过42℃热应激处理15min,每天间隔处理3次,连续处理7d,结束后每组取3只SD大鼠采集肌肉组织进行启动子甲基化检测,随后利用生物信息学软件预测SD大鼠肌肉组织中PGC-1α基因的CpG岛,针对CpG岛设计检测引物,采用重亚硫酸盐的测序法分析肌肉组织内PGC-1α基因启动子区CpG岛的甲基化程度,同时采用Western Blot法检测PGC-1α蛋白表达情况。将每组的另3只大鼠进行跑台一次性力竭运动,记录力竭时间。结果:热预适应处理显著延缓了运动疲劳的发生。同时,与对照组PGC-1α基因启动子区域CpG岛高度甲基化(50.20%±3.13%或48.78%±3.38%)相比,热预适应处理显著降低了PGC-1α基因的甲基化(18.57%±2.12%或19.80%±1.99%),但热预适应组PGC-1α基因的蛋白表达量却显著高于对照组。因此,SD大鼠在1w的热预适应过程中PGC-1α基因启动子区CpG岛的甲基化模式发生了显著变化,即随着热预适应处理时间的增加,PGC-1α基因启动子区甲基化程度逐渐降低,但PGC-1α基因的表达量显著升高。结论:对大鼠进行热预适应处理可以通过降低PGC-1α启动子的甲基化水平增加PGC-1α基因的表达量,这可能是热预适应通过PGC-1α基因启动子甲基化水平的改变延缓运动疲劳发生的机制之一。Objective:To investigate the mechanism of heat pre-adaptation-induce delaying of exercise fatigue by regulating the promoter methylation modification of peroxisomeproliferator-activated receptor-γcoactivator-1α(PGC-1α).Method:Twelve male Sprague Dawley rats(SD rats)of 8 weeks old were randomly divided into two groups:the heat pre-adaptation group(n=6)and the normal control group(n=6).The heat pre-adaptation group was treated with heat shock at 42℃for 15 min,3 times a day,and 7 days continuously.After that,muscle tissue was collected in 3 rats of each group for promoter methylation detection,and then the PGC-1αgene in the muscle tissue was predicted by bioinformatics software.The methylation degree of CpG island in the promoter region of PGC-1αgene was analyzed by bisulfite sequencing,and the change of PGC-1αprotein content was detected by Western Blot.The other three rats in each group ran on the treadmill and the exhaustion time was recorded.Result:The heat pre-adaptation significantly delayed the occurrence of exercise fatigue.At the same time,the results showed that the heat pre-adaptation significantly reduced the methylation of PGC-1αgene(18.57%±2.12%or 19.80%±1.99%),when compared that in the the control group(50.20%±3.13%or 48.78%±3.38%).However,the protein expression of PGC-1αgene in the heat pre-adaptation group was significantly higher than that in the control group.Therefore,the methylation pattern of CpG island in PGC-1αgene promoter region changed significantly during one week of heat pre-adaptation.With the increase of heat pre-adaptation time,the methylation degree of PGC-1αgene promoter region decreased gradually,while the expression of PGC-1αgene increased significantly.Conclusion:These results indicate that heat pre-adaptation can increase the expression of PGC-1αgene by reducing the methylation level of PGC-1αpromoter,which may be one of the mechanisms of heat pre-adaptation delaying the occurrence of exercise fatigue by changing the methylation level of PGC-1αpromoter.

关 键 词：过氧化物酶体增殖物活化受体γ协同刺激因子-1α 运动疲劳 热预适应 CPG岛 甲基化 

分 类 号：R493[医药卫生—康复医学]