Mesh : Animals Printing, Three-Dimensional Muscle, Skeletal / pathology Mice Muscular Atrophy / pathology etiology therapy Disease Models, Animal Male Muscular Disorders, Atrophic / pathology therapy Hindlimb Suspension / adverse effects Mice, Inbred C57BL

来  源:   DOI:10.1371/journal.pone.0304380   PDF(Pubmed)

Abstract:
Skeletal muscle atrophy is characterized by a decrease in muscle mass and strength caused by an imbalance in protein synthesis and degradation. This process naturally occurs upon reduced or absent physical activity, often related to illness, forced bed rest, or unhealthy lifestyles. Currently, no treatment is available for atrophy, and it can only be prevented by overloading exercise, causing severe problems for patients who cannot exercise due to chronic diseases, disabilities, or being bedridden. The two murine models commonly used to induce muscle atrophy are hindlimb suspension and ankle joint immobilization, both of which come with criticalities. The lack of treatments and the relevance of this atrophic process require a unilateral, safe, and robust model to induce muscle atrophy. In this work, we designed and developed a 3D-printed cast to be used for the study of disuse skeletal muscle atrophy. Applying two halves of the cast is non-invasive, producing little to no swelling or skin damage. The application of the cast induces, in 2-weeks immobilized leg, the activation of atrophy-related genes, causing a muscle weight loss up to 25% in the gastrocnemius muscle, and 31% in the soleus muscle of the immobilized leg compared to the control leg. The cross-sectional area of the fibers is decreased by 31% and 34% respectively, with a peculiar effect on fiber types. In the immobilized gastrocnemius, absolute muscle force is reduced by 38%, while normalized force is reduced by 16%. The contralateral leg did not show signs of overload or hypertrophy when compared to free roaming littermates, offering a good internal control over the immobilized limb. Upon removing the cast, the mice effectively recovered mass and force in 3 weeks.
摘要:
骨骼肌萎缩的特征在于由蛋白质合成和降解的不平衡引起的肌肉质量和力量的降低。这个过程自然发生在减少或缺乏体力活动,通常与疾病有关,强制卧床休息,或者不健康的生活方式.目前,没有治疗萎缩的方法,只有通过超负荷运动才能防止,对因慢性病而不能锻炼的患者造成严重问题,残疾人,或者卧床不起.两种常用的诱发肌肉萎缩的小鼠模型是后肢悬吊和踝关节固定,两者都带有关键性。缺乏治疗和这种萎缩过程的相关性需要单方面的,安全,和鲁棒模型来诱导肌肉萎缩。在这项工作中,我们设计并开发了一种3D打印模型,用于研究废用骨骼肌萎缩。施涂两半石膏是非侵入性的,产生很少或没有肿胀或皮肤损伤。铸造的应用诱导,在固定腿两周后,萎缩相关基因的激活,导致腓肠肌的肌肉体重减轻高达25%,与对照腿相比,固定腿的比目鱼肌中占31%。纤维的横截面积分别减少了31%和34%,对纤维类型有特殊的影响。在固定的腓肠肌中,绝对肌肉力量减少了38%,而归一化力降低16%。与自由漫游的同窝者相比,对侧腿没有显示出超负荷或肥大的迹象。对固定肢体提供良好的内部控制。移除铸件后,小鼠在3周内有效恢复了质量和力量。
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