【摘要】 目的:通过观察一周注射PI3K阻断剂和跑台运动对mTOR及其下游信号的影响,深入探讨PI3K对运动骨骼肌蛋白合成信号的机理。方法:8周龄雄性SD鼠在适应性训练后分为四组:安静组(S)、阻断剂组(SL)、运动组(E)、运动+阻断剂组(EL),每组6只。运动方式为跑台运动(坡度为10%,跑速20m/min,60min),每天一次,共7天。腹腔注射外源性LY294002。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,LY294002明显抑制MHC,运动有促进的趋势,并减弱LY294002对MHC的抑制效应。LY294002显著抑制mTOR(Ser2448)、p70S6K(Thr 389)和4EBP1(Thr 37/46)的磷酸化表达,而运动明显增强其表达。外源性LY294002和运动因素间存在交互效应,LY294002减弱运动对此通路的促进效应。结论:1)一周外源性PI3K阻断剂注射明显抑制mTOR及下游信号,并能显著抑制运动所引起的蛋白促合成效应。2)mTOR的两个下游信号对运动均较敏感,但4EBP1对PI3K阻断剂的反应较为迟钝。更多还原

【Abstract】 Aim: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 blocking PI3K in vivo.Methods:adult male Sprague-Dawley rats(8 weeks old) were randomly divided into 4 groups after adaptive training:sedentary(S),LY294002 group(SL),exercise group(E) and LY294002 plus exercise group(EL).The following treadmill training was applied:20m/min at 10% slope,60 min;once per day,7 days.Rats were treated daily with Either 8% ethanol or LY294002(5.5mg/kg,diluted with 8% ethanol) intraperitoneal injection 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,MHC was significantly inhibited by LY294002.Exercise had a tendency to increase MHC,and it attenuated the inhibitory effect of LY294002 on MHC.Phosphorylation of mTOR(Ser2448)(P<0.01),p70S6K(Thr389) and 4EBP1(Thr37/46) were significantly inhibited by LY294002,but they were elevated by exercise.Exercise had synergy effect with blocking PI3K in vivo.And exercise could attenuate the inhibitory effect of LY294002.Conclusions:these results suggest that:1) The phosphorylation of mTOR and downstreams of mTOR of skeletal muscle was inhibited significantly by blocking on PI3K,and attenuated the effect of exercise in vivo.2) Downstreams of mTOR were all sensitive to exercise,but 4EBP1 was little sensitive to blocking on PI3K.更多还原