PGC-1a信号级联在运动强度改善心肺耐力中的剂量-效应特征及调控机制研究

It is potential for good or evil, both of excessive and inadequate exercise will cause health risk. It is important and difficult how to carry out scientific and effective exercise for current development of national fitness and health. In view of cardiorespiratory fitness(CRF) recognized as important predictor of metabolism disease risk factors, and the dose-response relationship between exercise intensity and CRF, the study provides dose-response as a breakthrough to investigate the mechanisms of skeletal muscle adaptation from the point of PGC-1a and mitochondrial biogenesis during exercise intensity improving CRF, which included as follow: (1) establish an intervention model make of a different dose of exercise intensity, and analysis the signal transduction pathway coupling mechanism of exercise--PGC-1a--mitochondrial biogenesis; (2) establish a one-time exhaustive exercise model, analysis the positive and negative feedback mechanisms of PGC-1a signaling cascade and mitochondrial biogenesis induced by exercise, and then confirming the signal transduction pathway regulatory mechanisms of exercise--PGC-1a --mitochondrial biogenesis. Through this project, it can be expected to provide a strong theoretical basis and experimental evidence for revealing the nature of sport to promote physical health, and propose a new direction for the future development of the national fitness and health.

运动是一把双刃剑。运动过量或不足，都会导致一些健康风险。如何开展科学、有效的健身运动是当前国民体质健康发展的重点和难点。鉴于心肺耐力是预测代谢性疾病风险的独立因素，而运动强度与心肺耐力水平呈剂量-效应关系。针对上述研究现状，本项目以剂量-效应关系为突破口，从线粒体生物合成和PGC-1a信号级联的角度研究运动强度改善心肺耐力的骨骼肌适应机制：（1）建立不同强度运动干预模型，研究运动--PGC-1a--线粒体生物合成信号转导通路的剂量-效应关系和偶联机制；（2）建立一次性力竭运动模型，采用药物结合运动的方法，研究运动诱导PGC-1a信号级联和线粒体生物合成的正负反馈机制，进一步验证运动--PGC-1a--线粒体生物合成信号转导通路的调控机制。通过本项目研究，为揭示运动促进体质健康的本质提供了有力的理论基础和实验依据，并为今后国民体质健康发展的研究提出了新的方向。

心肺耐力是预测代谢性疾病风险的独立因素，探讨运动改善心肺耐力的生理学机制，对于如何开展科学、有效的健身运动具有重要的意义。本项目以剂量-效应关系贯穿全程，结合药物模拟运动的方法，开展运动强度、CRF、线粒体生物合成以及PGC-1a信号级联联动效应的一系列研究，结果表明：（1）不同强度运动引起VO2max和PGC-1a蛋白表达均呈剂量-效应关系；（2）不同强度诱导SIRT1蛋白表达与PGC-1a蛋白表达呈剂量-效应关系，而AMPK总蛋白表达变化不大，磷酸化AMPK表达是随着强度越大提高越显著，提示AMPK--SIRT1--PGC-1a参与了运动强度诱导PGC-1a表达/活性的上游信号转导通路的剂量依赖和效应表达；（3）单纯注射AICAR，PGC-1a表达显著升高，运动+AICAR时，中等强度和大强度组PGC-1a蛋白表达均呈显著性下降，即在激动剂+运动的情况下，反而抑制了PGC-1a的表达。本课题的研究成果将为进一步研究开展运动改善心肺耐力的骨骼肌适应提供了参考和借鉴。项目执行期内共发表与本课题（基金号31401017）相关的论文7篇，其中SCI论文2篇，中文核心期刊5篇。