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在大鼠比目鱼肌反复进行离心运动期间 IGF1/Akt/mTOR/p70s6k 通路激活的时程变化。

Time Course Change of IGF1/Akt/mTOR/p70s6k Pathway Activation in Rat Gastrocnemius Muscle During Repeated Bouts of Eccentric Exercise.

机构信息

Laboratory of Health and Sports Sciences, Center for Liberal Arts, Meiji Gakuin University.

出版信息

J Sports Sci Med. 2010 Jun 1;9(2):170-5. eCollection 2010.

PMID:24149682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3761746/
Abstract

The purpose of this study was to examine whether insulin-like growth factor (IGF-1) and Akt/mTOR/p70S6K pathway activity is altered by chronic eccentric exercise in rat medial gastrocnemius muscle. Male Wistar rats (n = 24) were randomly assigned to 1 of the 2 groups: eccentric exercise (ECC) group or sham-operated control (CON) group. Rats in the ECC group were trained every second day for 10 days (5 sessions in total) or 20 days (10 sessions in total). After either 5 or 10 exercise sessions, muscle specimens were dissected and weighed. The mRNA expression of IGF-1 and its variant, mechano growth factor (MGF), was evaluated using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Tissue concentrations of Akt (P), mTOR (P), and p70S6K (P) were measured by using western blot analysis. The medial gastrocnemius muscle mass of the ECC group did not show any significant difference after 5 exercise sessions, whereas the muscle mass increased significantly after 10 exercise sessions with a concomitant increase in the cross-sectional area of muscle fibers (p < 0.05). The expression of IGF-1 mRNA and the tissue concentrations of Akt (P) and p70S6K (P) after 10 exercise sessions was significantly higher than those of the age-matched controls and the rats that received 5 exercise sessions. The expression of MGF mRNA in both ECC5S and ECC10S were significantly higher than that in each period-matched control (p < 0.01). The tissue concentration of mTOR (P) after 10 sessions showed a significant increase when compared with period-matched controls (p < 0.01). These results suggest that activation of the IGF-1/Akt/mTOR/p70S6K signaling pathway becomes dominant in the later phase of chronic exercise, when significant muscular hypertrophy is observed. Key pointsWe confirmed that the rat muscular exercise model using originally-developed equipment increased the wet mass of the medial gastrocnemius muscle and cross-sectional areas of muscle fibres in 10 sessions (20 days) but not in 5 sessions (10days).We clarified that the increases of muscle mass and CSA of muscle fibers were accompanied by IGF-1 mRNA expression, the phosphorylated Akt, mTOR, and p70S6K.These results suggest that muscular hypertrophy in our model was achieved after 10 sessions of exercise and associated with the activation of IGF-1/Akt/mTOR/p70S6K signal pathway.

摘要

本研究旨在探讨胰岛素样生长因子 (IGF-1) 和 Akt/mTOR/p70S6K 通路活性是否会因慢性离心运动而改变大鼠内侧比目鱼肌。雄性 Wistar 大鼠(n = 24)随机分为 2 组之一:离心运动(ECC)组或假手术对照(CON)组。ECC 组大鼠每隔一天训练 10 天(共 5 次)或 20 天(共 10 次)。在 5 次或 10 次运动后,解剖并称重肌肉标本。使用实时逆转录聚合酶链反应 (RT-PCR) 评估 IGF-1 及其变体机械生长因子 (MGF) 的 mRNA 表达。使用 Western blot 分析测定 Akt(P)、mTOR(P)和 p70S6K(P)的组织浓度。ECC 组的内侧比目鱼肌在 5 次运动后没有显示出任何明显的差异,而在 10 次运动后肌肉量显著增加,同时肌肉纤维的横截面积增加(p < 0.05)。10 次运动后 IGF-1 mRNA 的表达以及 Akt(P)和 p70S6K(P)的组织浓度明显高于年龄匹配的对照组和接受 5 次运动的大鼠。ECC5S 和 ECC10S 中的 MGF mRNA 表达均明显高于每个时期匹配的对照组(p < 0.01)。与时期匹配的对照组相比,10 次运动后的 mTOR(P)组织浓度显著增加(p < 0.01)。这些结果表明,当观察到明显的肌肉肥大时,IGF-1/Akt/mTOR/p70S6K 信号通路的激活在慢性运动的后期阶段变得占主导地位。关键点我们证实,使用原创设备的大鼠肌肉运动模型在 10 次(20 天)而不是 5 次(10 天)增加了内侧比目鱼肌的湿重和肌肉纤维的横截面积。我们阐明了肌肉质量和肌肉纤维 CSA 的增加伴随着 IGF-1 mRNA 表达、磷酸化 Akt、mTOR 和 p70S6K 的增加。这些结果表明,我们模型中的肌肉肥大是在 10 次运动后实现的,并与 IGF-1/Akt/mTOR/p70S6K 信号通路的激活有关。

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