CAJ | 학술논문

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p38MAPK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％VO2 max，5°，15m／min，45min，每阔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；p38MAPK和p-p38MAPK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p38MAPK、p-p38MAPK、COXIV蛋白间均有显著正相关；H2O2与p-p38MAPK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；p38MAPK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p38MAPK、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。
목적：관찰대서증령과정중골격기선립체생물합성적변화특점급작용여의의，천명p38MAPK신호통로재장기내력훈련대증령대서골격기선립체생물합성유도작용중적분자궤리급기생물학효응。방법：중등강도포태운동（64％VO2 max，5°，15m／min，45min，매활5천）시가우2、12화17월령웅성대서공12주（매조8지）。상동월령대조조정상사양。12주후취대서Ⅰ형기섬유분별진행선립체형태학、지질과양화급삼여생물합성적전록인자분자생물학지표적검측。결과：골격기선립체생물합성수증령개변，내력훈련가이현저증가각월령조불동부위선립체적수밀도화체밀도；선립체H2O2화MDA수증령생성증다，내력훈련가이개선기양화환원상태；p38MAPK화p-p38MAPK표체수증령증가，PGC-1α표체하강。내력훈련후저사선립체단백화전록인자표체재불동월령조증가정도불동。PGC-1α여p38MAPK、p-p38MAPK、COXIV단백간균유현저정상관；H2O2여p-p38MAPK단백재대조조존재현저정상관。결론：대서증령과정중골격기선립체체밀도화수밀도증가；p38MAPK적린산화가능시수축활동도치선립체생물합성적일개중요신호통로，선립체산생적H2O2가능개도료저일과정；내력훈련능구유도p38MAPK、PGC-1α표체증가，종이촉진골격기선립체생물합성，개선선립체양화환원상태，종이저항골격기적증령성변화。
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 respiration may be involved in this process. 3. Endurance training significantly enhanced the skeletal muscle mitochondrial biogenesis through the increase expression of PGC-1α and p38MAPK proteins, resulting in improving mitochondrial redox state and delay aging process of skeletal muscle.