外源性IGF-I对大鼠运动骨骼肌mTOR及下游信号的影响

Effects of Exogenous IGF-I and Exercise on mTOR and Downstreams of mTOR of Skeletal Muscle in Rats

目的:通过观察一周注射外源性IGF-I和跑台运动对mTOR及其下游信号的影响,以深入探讨IGF-I对运动骨骼肌蛋白合成信号的影响机理。方法:8周龄雄性SD鼠在适应性训练后分为四组:安静组(S)、IGF-I组(SI)、运动组(E)、运动+IGF-I组(EI),每组6只。运动方式为跑台运动(坡度为10%,跑速20 m/min,60min),每天一次,共7 d。外源性IGF-I为小腿后侧肌肉隆起处的皮下注射。用Western Blotting法检测腓肠肌MHC、mTOR(Ser2448)、p70S6K(Thr389)和4EBP1(Thr37/46)的磷酸化表达。结果:在一周后,外源性IGF-I显著促进骨骼肌湿重和MHC的表达。外源性IGF-I和运动均显著促进骨骼肌mTOR(Ser 2448)(P<0.01)、p70S6K(Thr 389)(P<0.01)和4EBP1(Thr 37/46)(P<0.01)的磷酸化表达。外源性IGF-I和运动因素在影响mTOR及其下游信号时存在协同促进效应。结论:1)一周外源性IGF-I注射明显促进骨骼肌蛋白合成,且明显强于运动的促合成效应。2)一周外源性IGF-I注射与运动均能明显促进运动骨骼肌mTOR及其下游信号的活性。

Objective：The purpose of this study was to examine the effect of mTOR and downstream of mTOR on muscle protein synthesis in resistance treadmill exercise model through injecting exogenous IGF-I in vivo.Methods： Adult male Sprague-Dawley rats（8 weeks old） were randomly divided into 4 groups after adaptive training： sedentary（S）,IGF-I group（SI）,exercise group（E） and IGF-I plus exercise group（EI）.The following treadmill training was applied： 20m/min at 10% slope,60 min;once per day,7 days.Rats were treated daily with IGF-I（5.5 mg/kg,diluted with saline） or saline local subcutaneously for 7 days.The MHC and phosphorylation of mammalian target of rapamycin（mTOR）（Ser2448）,70-kDa ribosomal protein S6 kinase（p70S6K）（Thr389）,eIF4E binding protein 1（4EBP1）（Thr37/46） of gastrocnemius muscle were determined by western blotting.Results： After 1 week,wet weight and MHC of gastrocnemius muscle was promoted significantly by exogenous IGF-I（P0.01）.Phosphorylation of mTOR（Ser2448）（P0.01）,p70S6K（Thr389） and 4EBP1（Thr37/46） were significantly promoted by exogenous IGF-I and exercise.Exercise had synergy effect with exogenous IGF-I in vivo.Conclusions：1） Exogenous IGF-I could effectively lead to muscular hypertrophy after one week injecting exogenous IGF-I.The effect of exogenous IGF-I was greater than exercise.2） The mTOR and downstream of mTOR of skeletal muscle was significantly promoted by exogenous IGF-I.