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氨基酸混合物对抗骨骼肌萎缩:对线粒体生物能学的影响。

An Amino Acid Mixture to Counteract Skeletal Muscle Atrophy: Impact on Mitochondrial Bioenergetics.

机构信息

Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

出版信息

Int J Mol Sci. 2024 May 31;25(11):6056. doi: 10.3390/ijms25116056.

Abstract

Skeletal muscle atrophy (SMA) is caused by a rise in muscle breakdown and a decline in protein synthesis, with a consequent loss of mass and function. This study characterized the effect of an amino acid mixture (AA) in models of SMA, focusing on mitochondria. C57/Bl6 mice underwent immobilization of one hindlimb (I) or cardiotoxin-induced muscle injury (C) and were compared with controls (CTRL). Mice were then administered AA in drinking water for 10 days and compared to a placebo group. With respect to CTRL, I and C reduced running time and distance, along with grip strength; however, the reduction was prevented by AA. Tibialis anterior (TA) muscles were used for histology and mitochondria isolation. I and C resulted in TA atrophy, characterized by a reduction in both wet weight and TA/body weight ratio and smaller myofibers than those of CTRL. Interestingly, these alterations were lightly observed in mice treated with AA. The mitochondrial yield from the TA of I and C mice was lower than that of CTRL but not in AA-treated mice. AA also preserved mitochondrial bioenergetics in TA muscle from I and C mice. To conclude, this study demonstrates that AA prevents loss of muscle mass and function in SMA by protecting mitochondria.

摘要

骨骼肌萎缩症(SMA)是由肌肉分解增加和蛋白质合成减少引起的,导致质量和功能丧失。本研究在 SMA 模型中对氨基酸混合物(AA)的作用进行了特征描述,重点是线粒体。C57/Bl6 小鼠的一条后腿(I)或肉毒毒素诱导的肌肉损伤(C)被固定,并与对照组(CTRL)进行比较。然后,将 AA 以饮用水的形式施用于小鼠 10 天,并与安慰剂组进行比较。与 CTRL 相比,I 和 C 减少了跑步时间和距离,以及握力;然而,AA 预防了这种减少。比目鱼肌(TA)用于组织学和线粒体分离。I 和 C 导致 TA 萎缩,其特征是湿重和 TA/体重比均降低,且肌纤维比 CTRL 小。有趣的是,在接受 AA 治疗的小鼠中,这些变化较轻。I 和 C 小鼠 TA 的线粒体产量低于 CTRL,但在 AA 治疗的小鼠中则没有。AA 还可以维持 I 和 C 小鼠 TA 肌肉的线粒体生物能。总之,本研究表明 AA 通过保护线粒体来防止 SMA 中肌肉质量和功能的丧失。

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