目的:旨在研究运动对AMPKα2三种不同基因状态鼠骨骼肌细胞核内HDAC5/PGC1-MEF2结合量的影响,以探讨运动提高骨骼肌MEF2-GLUT4 DNA结合活性的可能机制。方法:野生鼠,AMPKα2基因高表达和敲除鼠各20只,分别随机分为安静对照组和跑台运动组,运动时间均为1 h,跑台速度为20 m/min。运动后3 h取材。结果:野生鼠1 h跑台运动后,骨骼肌细胞核内HDAC5与MEF2结合量显著减低,而PGC1和MEF2结合量显著升高;AMPKα2基因高表达及敲除鼠骨骼肌细胞核内HDAC5与MEF2结合量与野生鼠相比均没有显著差异,AMPKα2基因高表达鼠骨骼肌细胞核内PGC1与MEF2结合量显著高于野生鼠。结论:运动可能通过减少骨骼肌细胞核内MEF2和HDAC5结合量,并提高MEF2和PGC1的结合量而调节MEF2/GLUT4结合活性;AMPKα2参与调解运动诱导的MEF2/GLUT4的结合活性的增加并不是通过降低HDAC5和MEF2结合量实现的,而是通过提高PGC1与MEF2结合量增多而实现。
Objective: The effects of exercise on the content of MEF2–bound HDAC5/PGC1 were investigated in skeletal muscle of AMPKα2-WT/KO/OE mice to explore the possible mechanism of improving the association activity of the MEF2-GLUT4 DNA of skeletal muscle.Methods: Wild-type(WT;n=20),AMPKα2 over-expression(OE;n=20) and knockout(KO;n=20) C57/BL mice were randomly subdivided into two groups: control group and exercise group.Mice were killed 3 h after treadmill running for 60 min at 20 m/min on the experimental day.Results: After one hour running exercise,MEF2–bound HDAC5 decreased,whereas MEF2–bound PGC1 increased in wild type mice.MEF2 bound HDAC5 was normal in α2-OE and α2-KO muscles after 1 hour exercise.MEF2-combined PGC1 in OE mice was higher than that in WT mice.Conclusion: Exercise increases binding of MEF2A binding by decreasing HDAC5-MEF2 complexes and increasing PGC1-MEF2 complexes;Exercise-induced AMPK activation increases the binding of MEF2A to the Glut4 promoter by a mechanism not involving the decreased nuclear HDAC5-MEF2 complexes,but involving the increased nuclear PGC-1 combined with MEF2.