不同模式的低氧训练对骨骼肌肌球蛋白合成及其mTOR信号通路的影响

The Effect of Hypoxia Training of Different Modes on Myosin Synthesis and mTOR Signaling Pathway in Skeletal Muscles

目的:探讨模拟高原训练和高住低练对大鼠骨骼肌蛋白质合成的影响和机制。方法:50只SD大鼠随机分成常氧对照组(NC,n=10)、低氧暴露组(HC,n=10)、常氧训练组(NE,n=10)、模拟高原训练组(HE,n=10)、高住低练组(HiLo,n=10)。通过人工低氧和游泳训练模拟高原训练和高住低练,6周后测定大鼠腓肠肌中总蛋白(Pro)和肌球蛋白(Myo)含量,同时测定腓肠肌中PI3K、Akt蛋白含量以及mTOR、真核细胞延伸因子2(eEF2)和真核细胞翻译起始因子4E结合蛋白1(4EBP-1)的m RNA表达。结果:(1)低氧暴露和大强度的运动训练均使Pro和Myo含量显著下降(P<0.05),低氧暴露与运动训练虽然对降低Pro含量无显著性交互作用,但对降低Myo含量有显著性的交互作用(P<0.05);HiLo组Pro和Myo含量显著低于NC组,而显著高于HE组(P<0.05)。(2)低氧暴露显著降低PI3K(P<0.05)、Akt含量和mTOR m RNA表达(P<0.01)的同时,显著升高4E-BP1 mRNA表达量(P<0.05);运动训练能显著降低PI3K含量(P<0.05)、mTOR mRNA(P<0.01)和eEF2 mRNA表达(P<0.05),显著升高4E-BP1 mRNA表达(P<0.05);低氧暴露与运动训练对进一步降低mTOR和eEF2 mRNA表达具有显著性的交互作用(P<0.01,P<0.05);与NC组相比,HiLo组PI3K、Akt含量和mTOR mRNA表达无显著性变化,而4E-BP1mRNA的表达显著升高;与HE组相比,HiLo组PI3K含量、mTOR和eEF2的mRNA表达显著升高(P<0.01)。结论:(1)低氧和大强度的运动训练能抑制骨骼肌PI3K/Akt/mTOR及其下游信号通路,导致骨骼肌蛋白质含量的降低。低氧联合大强度运动训练在一定程度上对骨骼肌PI3K/Akt/mTOR及其下游信号通路的抑制作用比单纯的低氧暴露或大强度运动训练更大。(2)高住低练能减轻骨骼肌中PI3K/Akt/mTOR及其下游信号通路的抑制程度,减轻抑制骨骼肌蛋白质合成的程度,对防止低氧引起的骨骼肌蛋白质的丢失具有重要作用。

Objective To explore the effect of the simulated altitude training and living high-training low(Hi-Lo) on the myosin synthesis in skeletal muscles of rats and its biochemical mechanism.Methods Fifty Sprague-Dawley rats were randomly divided into a normoxic control group(NC,n=10),a hypoxic control group(HC,n=10),a normoxic training group(NE,n=10),a simulated altitude training group(HE,n=10) and an HiLo group(n=10).The content of total protein(Pro),myosin(Myo),PI3 K,AKT and the m RNA expression of mTOR,eu-karyotic elongation factor 2(eEF2) and eukaryotic translation initiation factor 4E binding protein 1(4EBP1) inthe gastrocnemius of rats were measured after 6 weeks of simulated altitude training or HiLo.Results The aver-age Pro and Myo content decreased significantly(P<0.05) after the hypoxic exposure and intensive exercise train-ing.There was a significant interaction of the hypoxic exposure with exercise training on reducing the Myo content(P<0.05),but not the Pro content.The average content of Pro and Myo in the HiLo group were significant-ly lower than NC group,but significantly higher than the HE group(P<0.05).Moreover,the hypoxic exposuresignificantly reduced the average content of PI3K(P<0.05), Akt(P<0.01) and mTOR m RNA expression(P<0.01),but significantly increased the 4E-BP1 mRNA expression(P<0.05).The exercise training significantly de-creased the average PI3 K content(P<0.05),mRNA expression of mTOR(P<0.01) and eEF2(P<0.05) but signifi-cantly increased the 4E-BP1 m RNA expression(P<0.05).There was a significant interaction of the hypoxic expo-sure and exercise training on reducing the mRNA expression of mTOR and eEF2(P<0.01,P<0.05).Comparedwith the NC group, no significant differences were observed in the average PI3 K, Akt content and mTORmRNA expression in the HiLo group,but the expression of 4E-BP1 m RNA increased significantly in the HiLogroup.However,the average PI3 K content and mRNA expression of mTOR and eEF2 of the HiLo group in-creased more significantly compared with the HE group(P<0.01).Conclusion Both hypoxic and intensive exer-cise training can reduce the protein content in skeletal muscle by inhibiting the PI3K/Akt/mTOR and its down-stream signaling pathways.To a certain extent,the inhibitory effect of the hypoxia combined with intensive exer-cise training on PI3K/Akt/mTOR and its downstream signaling pathways in skeletal muscle is greater than thatof simple hypoxic exposure or intensive exercise training.Living high-training low can reduce the inhibition ofPI3K/Akt/mTOR and its downstream signaling pathways in skeletal muscle and reduce the degree of inhibitionof skeletal muscle protein synthesis,which plays an important role in preventing the loss of skeletal muscle pro-tein caused by hypoxia.