耐力训练诱导增龄大鼠骨骼肌线粒体生物合成:ROS介导的p38 MAPK信号通路  

Muscular Mitochondria Biogenesis Induced by Endurance Training in Aged Rat:p38 MAPK Signaling Pathway Regulated by Reactive Oxygen Species

作　　者：韩雨梅[1,2] 刘子泉[1] 常永霞[1] 刘树森[3] 吉力立[4] 张勇[1] 

机构地区：[1]天津体育学院天津市运动生理学与运动医学重点实验室,天津300381 [2]山西大学体育学院,山西太原030006 [3]中国科学院动物研究所生物膜与膜生物工程国家重点实验室,北京100101 [4]威斯康辛大学运动学系,美国威斯康辛53706

出　　处：《体育科学》2009年第11期48-53,58,共7页China Sport Science

基　　金：国家自然科学基金(30470837);天津市社会发展重大科技攻关项目(05YFGDSF02100)

摘　　要：目的:观察大鼠增龄过程中骨骼肌线粒体生物合成的变化特点及作用与意义,阐明p38 MAPK信号通路在长期耐力训练对增龄大鼠骨骼肌线粒体生物合成诱导作用中的分子机理及其生物学效应。方法:中等强度跑台运动(64%.VO2max,5°,15m/min,45min,每周5天)施加于2、12和17月龄雄性大鼠共12周(每组8只)。相同月龄对照组正常饲养。12周后取大鼠Ⅰ型肌纤维分别进行线粒体形态学、脂质过氧化及参与生物合成的转录因子分子生物学指标的检测。结果:骨骼肌线粒体生物合成随增龄改变,耐力训练可以显著增加各月龄组不同部位线粒体的数密度和体密度;线粒体H2O2和MDA随增龄生成增多,耐力训练可以改善其氧化还原状态;p38 MAPK和p-p38 MAPK表达随增龄增加,PGC-1α表达下降。耐力训练后这些线粒体蛋白和转录因子表达在不同月龄组增加程度不同。PGC-1α与p38 MAPK、p-p38 MAPK、COXIV蛋白间均有显著正相关;H2O2与p-p38 MAPK蛋白在对照组存在显著正相关。结论:大鼠增龄过程中骨骼肌线粒体体密度和数密度增加;p38 MAPK的磷酸化可能是收缩活动导致线粒体生物合成的一个重要信号通路,线粒体产生的H2O2可能介导了这一过程;耐力训练能够诱导p38 MAPK、PGC-1α表达增加,从而促进骨骼肌线粒体生物合成,改善线粒体氧化还原状态,从而抵抗骨骼肌的增龄性变化。Objective：The purpose of this study was to investigate the feature of mitochondrial biogenesis of skeletal muscle and its contribution in aging process, and explore the molecular mechanism of p38 MAPK and the biological significance involved in exercise-induced mitochon- drial biogenesis in aging. Method ： Moderate endurance training （ 64% VO2 peak） was imposed on the groups of rats aged 2,12 and 17 months as training in a treadmill （5 °, 15 m/min, 45 min, every 5 days） for 12 weeks, respectively. The control rats remained sedentary. After the 12 weeks training treatment and 24 hours after training, the rats were anesthetized, and the skeletal muscle （type Ⅰ ） was rapidly excised to test the parameters in mitoehondrial ultramorphology, ROS generation, also mitochondrial protein and transcription factor expression in mitochondrial biogenesis. Result： 1. Mitochondria biogenesis changed in aging rat skeletal muscle, endurance training induced increase in number density and volume density of mitochondrial different regions in all groups. 2. Mitochondrial ROS and MDA generation increased during the aging. Endurance training improved the redox state in mitochondria. 3. The expression of p38MAPK and p-p38MAPK involved in the mitochondrial biogenesis increased during the aging process, PGC-1α protein content decreased with the aging. Endurance training did induce the significant expression of these transcriptional factors and mitochondrial proteins, especially in young age. 4. Correlative analysis showed that there was a remarkable positive correlation between PGC-1α protein content and p38MAPK, p-p38MAPK and COXIV respectively, same as between H2O2 and p-p38MAPK protein content in control group. Conclusion： 1. Volume density and number density of mitochondrial were also found to be increased during rat aging. 2. The phosphorylation of p38MAPK probably is a key mediator in the contractile activity-induced mitochondrial biogenesis in rat skeletal muscle and H2O2 generated in mitochondrial respira

关 键 词：耐力训练 骨骼肌 线粒体生物合成 P38 MAPK 增龄 鼠 动物实验 

分 类 号：G804.7[文化科学—运动人体科学]