运动、IGF-Ⅰ诱导骨骼肌适应性肥大的机理研究

Mechanism of Exercise and IGF-Ⅰ Inducing Skeletal Muscle Adaptive Hypertrophy in Rats

目的:采用注射外源性IGF-I和一周跑台运动,观察对大鼠骨骼肌mTOR信号通路的影响,深入探讨IGF-I对运动骨骼肌适应性肥大的机理。方法:8周龄雄性SD大鼠在适应性训练后分为四组:安静组(S)、安静IGF-I组(SI)、运动组(E)、运动+IGF-I组(EI)。运动方式为跑台运动(20m/min,10%,60min/d),每天一次,共7天。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、PI3K、AKt、mTOR、p70S6K蛋白和Akt(Ser473)、mTOR(Ser2448)和p70S6K(Thr389)的磷酸化表达。结果:在一周后,外源性IGF-I显著促进骨骼肌MHC的表达,骨骼肌PI3K、Akt、mTOR蛋白和Akt(Ser473)、mTOR(Ser2448)和p70S6K(Thr389)的磷酸化表达显著增强。运动显著促进mTOR蛋白和Akt(Ser473)、mTOR(Ser2448)和p70S6K(Thr389)磷酸化的表达。对运动的反应,上述信号的磷酸化表达高于蛋白表达。结论:1)一周外源性IGF-I注射明显促进运动骨骼肌mTOR通路的活性;而1周跑台运动与IGF-I具有协同增强效应。2)在运动和注射外源性IGF-I的刺激下,mTOR通路各信号分子的磷酸化表达比蛋白表达更为敏感。建议今后对信号的研究以检测信号分子的磷酸化表达为主。

Objective：the purpose of this study was to examine the effect of mTOR signal pathway on Skeletal Muscle A- daptive Hypertrophy 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 （El）. The following treadmill training was appLied.20m/mit~ at 10% slope, 60 min;once per day,7 days. Rats were treated daily with exogenous IGF-I （5.5 mg/kg, diluted with saline） or saline local subcutaneously for 7 days. The MHC, PI3K, AKt and phosphorylation of Akt（ Ser473 ）, mammalian target of rapamycin（roTOR） and phosphorylation of roTOR（ Ser2448 ） ,p70s6K and phosphorylation of p70s6K （ Thr 389 ） of gastroc- nemius muscle were determined by Western blotting. Results：After 1 week, wet weight and MHC of gastrocnemius muscle was promoted significantly by IGF-I, PI3K, AKt and phosphorylation of Akt（ Ser473 ）, mTOR and phosphorylation of mTOR（ Ser2448 ）, p70s6K and phosphorylation of p70s6K （ Thr 389 ） were significantly promoted by IGF-I, and but they were elevated by exercise except PI3K. Conclusions：These results suggest that：l ） The mTOR pathway of skeletal muscle was significantly promoted by exogenous IGF-I, and the positive effect was global. Exercise had synergy effect with exogenous IGF-I in vivo ,while exercise can synergy improve mTOR pathway with IGF-I. The effect of exercise was particular empha- sis on partial elements of mTOR pathway. 2） Phosphorylations of mTOR pathway were sensitive than total-molecules.