低氧和运动对骨骼肌PKB/mTOR信号通路的影响
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摘要
目的:为探讨运动和低氧对骨骼肌蛋白质合成的影响和调控机制,本文研究了运动和低氧对肌肉生长的正负调控因子IGF-1、Myostatin表达和PKB/mTOR信号通路的影响。
方法:以SD大鼠为研究对象,随机分为常氧对照组、常氧运动组、低氧暴露组、高住低训组4大组。低氧暴露方式为每天晚上在氧浓度13.6%的低氧舱内低氧暴露12小时,白天为常氧环境的间歇性低氧暴露方式。运动方式为坡度5°,上坡跑,速度20米/分,每次60分钟,1次/天,6天/周的跑台运动。常氧下运动后1小时高住低训组再继续进行低氧暴露12小时。常氧运动组、高住低训组分别进行1天、28天和(或)复氧7天的运动和(或)低氧暴露。采用RT-PCR方法、ELISA和western等方法分别检测大鼠腓肠肌中IGF-1、Myostatin,PKB、mTOR、p70S6K的表达水平。
结果:(1) 28天高住低训组大鼠体重和骨骼肌质量显著下降,骨骼肌蛋白含量有下降趋势。(2) 28天高住低训组骨骼肌IGF-1蛋白表达显著下降(p<0.05)、Myostatin蛋白表达显著上升(p<0.05)。(3) 28天常氧运动组骨骼肌磷酸化PKB、mTOR和p70S6K蛋白表达都显著上升(p<0.05);(4) 28天高住低训组骨骼肌mTOR表达显著下降,p70S6K蛋白表达无变化,而复氧7天后表达都显著上升(p<0.05)。
结论:(1)运动和低氧暴露抑制骨骼肌蛋白合成,其机制可能是通过调节mTOR信号通路进行的。(2) IGF-1和Myostatin以相反的作用共同参与运动和低氧对骨骼肌生长和蛋白质代谢的调控。(3)运动和低氧调控mTOR信号可能存在IGF-1参与的PKB/mTOR途径和非IGF-1参与的其它途径。
Aims:To study the effect and mechanism of hypoxic exercise on protein synthesis in skeletal muscle,it tested the effect of exercise and hypoxia on IGF-1 and Myostatin expression which are positive and negative regulating factor of muscle growth,and the influence on PKB/mTOR signal pathway.
Materials and methods:SD rats were randomly divided into four groups: normoxia control group,normoxic exercise group,hypoxic exposure group, living high training low(HiLo) group.Hypoxic exposure treatment consisted of intermittent hypoxia with 13.6%concentrations of oxygen for 12 h/day under normobaric conditions in hypoxic chamber,and the training protocol consisted of treadmill running with 5°incline,20 m/min,1 h/day,1 time/day,6 days/wk.One hour after the exercise under normoxic condition,the HiLo group rats were exposed to hypoxia under normobaric condition for 12 h.1 day、28 days of exercise and(or) intermittent hypoxia exposure,7 days of reoxygen and exercise are carried out in the HiLo group and the normoxic exercise group.IGF-1、Myostatin,PKB、mTOR、p70S6E expression in gastrocnemius muscle were tested with the method of RT-PCR、ELISA、western blot.
Results:(1) After exercise and hypoxia exposure for 28 days,the HiLo group rats body weight,muscle mass and total protein content had been the decreased tendency;(2) After exercise and hypoxic exposure for 28 days,IGF-1 protein expression in muscle decreased significantly, myostatin protein expression increased significantly in the HiLo group (p＜0.05);(3) After 28 days exercise,phosphorylated PKB protein、mTOR and p70S6K protein expression in muscle increased significantly; (4)After living high training low for 28 days,mTOR protein expression in muscle had no change,but increased significantly after 7 days reoxygen.
Conclusions:(1) Exercise followed by hypoxia repress muscle protein synthesis,and its mechanism may be the way of regulation of mTOR signal in skeletal muscle by exercise and hypoxia.(2) In the condition of exercise and hypoxia,IGF-1 and Myostatin expression have complete contrast changes and involed in the regulation of growth of muscle and metabolism of muscle protein by exercise and hypoxia together.(3) It maybe the PKB/mTOR signaling pathway involved in IGF-1 and others pathway not involved in IGF-1 that exercise and hypoxia regulate mTOR signal.
方法:以SD大鼠为研究对象,随机分为常氧对照组、常氧运动组、低氧暴露组、高住低训组4大组。低氧暴露方式为每天晚上在氧浓度13.6%的低氧舱内低氧暴露12小时,白天为常氧环境的间歇性低氧暴露方式。运动方式为坡度5°,上坡跑,速度20米/分,每次60分钟,1次/天,6天/周的跑台运动。常氧下运动后1小时高住低训组再继续进行低氧暴露12小时。常氧运动组、高住低训组分别进行1天、28天和(或)复氧7天的运动和(或)低氧暴露。采用RT-PCR方法、ELISA和western等方法分别检测大鼠腓肠肌中IGF-1、Myostatin,PKB、mTOR、p70S6K的表达水平。
结果:(1) 28天高住低训组大鼠体重和骨骼肌质量显著下降,骨骼肌蛋白含量有下降趋势。(2) 28天高住低训组骨骼肌IGF-1蛋白表达显著下降(p<0.05)、Myostatin蛋白表达显著上升(p<0.05)。(3) 28天常氧运动组骨骼肌磷酸化PKB、mTOR和p70S6K蛋白表达都显著上升(p<0.05);(4) 28天高住低训组骨骼肌mTOR表达显著下降,p70S6K蛋白表达无变化,而复氧7天后表达都显著上升(p<0.05)。
结论:(1)运动和低氧暴露抑制骨骼肌蛋白合成,其机制可能是通过调节mTOR信号通路进行的。(2) IGF-1和Myostatin以相反的作用共同参与运动和低氧对骨骼肌生长和蛋白质代谢的调控。(3)运动和低氧调控mTOR信号可能存在IGF-1参与的PKB/mTOR途径和非IGF-1参与的其它途径。
Aims:To study the effect and mechanism of hypoxic exercise on protein synthesis in skeletal muscle,it tested the effect of exercise and hypoxia on IGF-1 and Myostatin expression which are positive and negative regulating factor of muscle growth,and the influence on PKB/mTOR signal pathway.
Materials and methods:SD rats were randomly divided into four groups: normoxia control group,normoxic exercise group,hypoxic exposure group, living high training low(HiLo) group.Hypoxic exposure treatment consisted of intermittent hypoxia with 13.6%concentrations of oxygen for 12 h/day under normobaric conditions in hypoxic chamber,and the training protocol consisted of treadmill running with 5°incline,20 m/min,1 h/day,1 time/day,6 days/wk.One hour after the exercise under normoxic condition,the HiLo group rats were exposed to hypoxia under normobaric condition for 12 h.1 day、28 days of exercise and(or) intermittent hypoxia exposure,7 days of reoxygen and exercise are carried out in the HiLo group and the normoxic exercise group.IGF-1、Myostatin,PKB、mTOR、p70S6E expression in gastrocnemius muscle were tested with the method of RT-PCR、ELISA、western blot.
Results:(1) After exercise and hypoxia exposure for 28 days,the HiLo group rats body weight,muscle mass and total protein content had been the decreased tendency;(2) After exercise and hypoxic exposure for 28 days,IGF-1 protein expression in muscle decreased significantly, myostatin protein expression increased significantly in the HiLo group (p＜0.05);(3) After 28 days exercise,phosphorylated PKB protein、mTOR and p70S6K protein expression in muscle increased significantly; (4)After living high training low for 28 days,mTOR protein expression in muscle had no change,but increased significantly after 7 days reoxygen.
Conclusions:(1) Exercise followed by hypoxia repress muscle protein synthesis,and its mechanism may be the way of regulation of mTOR signal in skeletal muscle by exercise and hypoxia.(2) In the condition of exercise and hypoxia,IGF-1 and Myostatin expression have complete contrast changes and involed in the regulation of growth of muscle and metabolism of muscle protein by exercise and hypoxia together.(3) It maybe the PKB/mTOR signaling pathway involved in IGF-1 and others pathway not involved in IGF-1 that exercise and hypoxia regulate mTOR signal.
引文
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