抗阻训练通过Akt-FoxO1通路抑制低氧诱导的骨骼肌萎缩  

Resistance Training Activated Akt-FoxO1 Pathway to Prevent Skeletal Muscle Atrophy Induced by Hypoxia

作　　者：于加倍 胡扬[1] 李燕春[1] 梅涛 韩天雨 白学成 付鹏宇[1] 朱镕鑫 车欣媛 YU Jia-Bei;HU Yang;Li Yan-Chun;MEI Tao;HAN Tian-Yu;BAI Xue-Cheng;FU Peng-Yu;ZHU Rong-Xin;CHE Xin-Yuan(Sports Biochemistry Teaching and Research Department of Human Sport Science,Beijing Sport University,Beijing 100084,China)

机构地区：[1]北京体育大学运动人体科学学院运动生化教研室,北京100084

出　　处：《中国生物化学与分子生物学报》2018年第10期1118-1126,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金面上项目(No.31771317)~~

摘　　要：高原低氧环境会引起肌力下降和运动能力退化,而抗阻训练是刺激骨骼肌生长的重要手段,叉头转录因子1(fork head box protein O 1,FoxO1)在调控骨骼肌蛋白质分解通路中承担重要角色。为探究Akt-FoxO1通路是否参与抗阻训练抑制低氧诱导的骨骼肌萎缩,本研究构建低氧诱导骨骼肌萎缩的大鼠模型,并模拟海拔4 000 m低氧环境下(12.4%O_2)进行抗阻训练,对比观察大鼠比目鱼肌和趾长伸肌湿重和横截面积,以及蛋白激酶B(protein kinase B,Akt)、叉头转录因子1、泛素蛋白连接酶1(muscle ring finger 1,MuRF1)的表达差异等。结果表明,低氧暴露导致大鼠趾长伸肌湿重显著下降,苏木精-伊红染色组织切片分析肌纤维横截面积、低氧环境下比目鱼肌横截面积明显下降,而低氧抗阻训练后趾长伸肌横截面积明显高于安静组。实时荧光定量PCR和蛋白质免疫印迹结果显示,低氧暴露后FoxO1和MuRF1基因表达明显上调,低氧下抗阻训练后发现,Akt基因表达明显上调而FoxO1、MuRF则明显下调。免疫荧光观察磷酸化FoxO1在细胞核内外表达情况,发现抗阻训练后FoxO1(S256)于细胞核外表达增强。上述结果表明,抗阻训练可以达到抑制低氧诱导骨骼肌萎缩的效果,Akt促进FoxO1磷酸化从而减缓骨骼肌蛋白质分解过程是抗阻训练能够抑制骨骼肌萎缩的分子机制之一。Skeletal muscle atrophy induced by hypoxia on the plateau will lead to the decrease of muscle strength and the degeneration of athletic ability. Resistance training is an important method to stimulate the growth of muscle and FoxO1 （Fork head box protein O1, FoxO1） plays a significant role in the regulation of skeletal muscle protein degradation pathway. However it is not clear how FoxO1 regulates skeletal muscle protein under the intervention of both hypoxia and resistance training. This study built a rat model that resistance training inhibited the skeletal muscle atrophy induced by hypoxia. Resistance training was carried out with simulated altitude of 4 000 m （12.4% O2）. Wet weight and cross sectional areas （CSA） of soleus and extensor digitorum longus （EDL） were measured and comparative observation of protein kinase B （Akt） , FoxO1, Ubiquitin protein ligase （muscle ring finger,MuRF） was obtained. The results showed that exposure to hypoxia for 4 weeks led to a decrease of muscle wet weight and CSA but resistance training could prevent the atrophy. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression of FoxO1 and MuRF of hypoxia group （ H group） were significantly higher than control group. However, after the intervention of resistance training, the expression of Akt was significantly up-regulated and FoxO1, MuRF were significantly down-regulated. Immunofluorescence technique was used to observe the location of FoxO1 phosphorylation and the expression out of nucleus. The results revealed that FoxO1 phosphorylation out of nucleus was increased after resistance training. All the above results revealed that resistance training could inhibit skeletal muscle atrophy induced by hypoxia. Akt promoted FoxO1 phosphorylation may become the molecular mechanisms that resistance training can inhibit the atrophy of skeletal muscle induced by hypoxia.

关 键 词：叉头转录因子1 低氧抗阻训练 骨骼肌萎缩 大鼠 

分 类 号：G804.7[文化科学—运动人体科学]