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赵海涛,曹庆雷,邓中原.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[J].中国康复医学杂志,2022,(10):1306~1311
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    点此下载全文
赵海涛  曹庆雷  邓中原
北京科技大学体育部,北京,100083
基金项目:
DOI:10.3969/j.issn.1001-1242.2022.10.003
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摘要:
      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-γ coactivator-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。
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
Study on the mechanism of PGC-1 α promoter methylation mediated by thermal pre adaptation in delaying exercise fatigue    Download Fulltext
Dept. of Physical Education,University of Science and Technology Beijing,100083
Fund Project:
Abstract:
      Abstract Objective: To investigate the mechanism of heat pre-adaptation-induce delaying of exercise fatigue by regulating the promoter methylation modification of peroxisomeproliferator-activated receptor-γ coactivator-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 15min, 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-1α gene in the muscle tissue was predicted by bioinformatics software. The methylation degree of CpG island in the promoter region of PGC-1α gene was analyzed by bisulfite sequencing, and the change of PGC-1α protein 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-1α gene (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-1α gene in the heat pre-adaptation group was significantly higher than that in the control group. Therefore,the methylation pattern of CpG island in PGC-1α gene promoter region changed significantly during one week of heat pre-adaptation. With the increase of heat pre-adaptation time, the methylation degree of PGC-1α gene promoter region decreased gradually,while the expression of PGC-1α gene increased significantly. Conclusion: These results indicate that heat pre-adaptation can increase the expression of PGC-1α gene by reducing the methylation level of PGC-1α promoter, which may be one of the mechanisms of heat pre-adaptation delaying the occurrence of exercise fatigue by changing the methylation level of PGC-1α promoter.
Keywords:peroxisome proliferator-activated receptor gamma-costimulatory factor-1α  exercise fatigue  thermal preconditioning  CpG island  methylation
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