Institute of Sports Biology, Shaanxi Normal University, Xi'an 710119, China.
Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University, Xi'an 710119, China.
Int J Mol Sci. 2021 Nov 9;22(22):12112. doi: 10.3390/ijms222212112.
Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm LIPUS irradiation group (UL + 30 mW/cm), hindlimb unloading plus 80 mW/cm LIPUS irradiation group (UL + 80 mW/cm). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm or 80 mW/cm for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.
低强度脉冲超声（LIPUS）已被证明可促进成肌细胞 C2C12 的增殖。然而，LIPUS 是否能有效预防肌肉萎缩尚不清楚，如果可以，其可能的机制是什么。本研究旨在评估 LIPUS 对后肢去负荷大鼠肌肉萎缩的影响，并探讨其机制。将大鼠随机分为四组：正常对照组（NC）、后肢去负荷组（UL）、后肢去负荷加 30 mW/cm LIPUS 照射组（UL + 30 mW/cm）、后肢去负荷加 80 mW/cm LIPUS 照射组（UL + 80 mW/cm）。后肢去负荷组大鼠尾巴悬吊 28 天。LIPUS 治疗组大鼠同时对双侧小腿腓肠肌进行 LIPUS 照射，声强 30 mW/cm 或 80 mW/cm，每天 20 分钟，共 28 天。C2C12 细胞在 30 或 80 mW/cm 下暴露 5 天。结果表明，LIPUS 显著促进成肌细胞 C2C12 的增殖和分化，并防止后肢去负荷大鼠腓肠肌横截面积和质量的减少。LIPUS 还显著下调 MSTN 及其受体 ActRIIB 的表达，并上调后肢去负荷大鼠腓肠肌中 Akt 和 mTOR 的表达。此外，选择三个代谢途径（苯丙氨酸、酪氨酸和色氨酸生物合成；丙氨酸、天冬氨酸和谷氨酸代谢；甘氨酸、丝氨酸和苏氨酸代谢）作为后肢去负荷效应的重要代谢途径。然而，LIPUS 促进了丙氨酸、天冬氨酸和谷氨酸代谢途径的稳定性。这些结果表明，LIPUS 预防后肢去负荷引起的肌肉萎缩的关键机制可能与通过 MSTN/Akt/mTOR 信号通路促进蛋白质合成以及稳定丙氨酸、天冬氨酸和谷氨酸代谢有关。
