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目的:通过建立不同运动负荷心肌肥大模型,探讨Akt/mTOR信号在运动性心肌肥大中的作用。方法:7周龄雄性SD大鼠在适应性训练后随机分为:安静对照组、中等强度组和大强度组。安静对照组6只,中等强度组和大强度组分别取4个观察点进行观察(末次运动后即刻、6 h、12 h和24 h),每个观测点6只。运动方案为递增负荷跑台训练,共进行7周。用Western blotting方法测定心肌Akt和mTOR蛋白表达,AktSer473和mTORSer2448磷酸化表达。结果:1)心脏重量系数:中等强度组和大强度组显著高于安静对照组,大强度组显著高于中等强度组。2)中等强度组心肌Akt蛋白和AktSer473磷酸化在运动后6 h达到峰值。mTOR蛋白表达和mTORSer2448磷酸化在运动后12 h达到峰值。大强度组心肌Akt和mTOR蛋白表达,AktSer473和mTORSer2448磷酸化表达在运动后即刻达到峰值。2个指标的磷酸化同总蛋白比值的变化趋势同各自磷酸化水平。结论:1)长期中等强度和大强度跑台训练可引起心肌肥大,肥大程度同运动负荷正相关。2)中等强度运动激活Akt/mTOR信号调控心肌肥大,而大强度运动未激活Akt/mTOR信号。3)运动负荷对Akt/mTOR信号调控存在级联关系,该信号通路的激活存在时间间隔。
OBJECTIVE: To investigate the role of Akt / mTOR signaling in exercise-induced cardiac hypertrophy by establishing cardiac hypertrophy models with different exercise loads. Methods: Seven-week-old male Sprague-Dawley rats were randomly divided into control group, moderate-intensity group and high-intensity group after adaptive training. Six rats in the quiet control group and four observation points in the middle-intensity group and the high-intensity group were observed (immediately after the last exercise, 6 h, 12 h and 24 h), and 6 in each observation point. Exercise program for incremental load treadmill training, a total of 7 weeks. Western blotting was used to determine the expression of Akt and mTOR proteins, phosphorylation of AktSer473 and mTORSer2448. Results: 1) Cardiac weight coefficient: the middle-intensity group and the high-intensity group were significantly higher than the quiet control group, the high-intensity group was significantly higher than the moderate-intensity group. 2) The intensity of myocardial Akt and AktSer473 phosphorylation peaked at 6 h after exercise in moderate intensity group. The mTOR protein expression and phosphorylation of mTORSer2448 peaked at 12 h after exercise. Myocardial Akt and mTOR protein expression in high-intensity group, phosphorylation of AktSer473 and mTORSer2448 peak immediately after exercise. The changes of the ratio of phosphorylation to total protein in the two indexes were the same as the respective phosphorylation levels. Conclusions: 1) Long-term moderate-intensity and high-intensity treadmill training can cause cardiac hypertrophy, and the degree of hypertrophy is positively correlated with exercise load. 2) Mid-intensity exercise activates Akt / mTOR signaling to control cardiac hypertrophy, whereas high-intensity exercise does not activate Akt / mTOR signaling. 3) The exercise load has a cascade relationship to the Akt / mTOR signaling regulation, and the activation of this signaling pathway has a time interval.