Inhibition of myostatin prevents microgravity-induced loss of skeletal muscle mass and strength
Inhibition of myostatin prevents microgravity-induced loss of skeletal muscle mass and strength
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DOI：
10.1371/journal.pone.0230818
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发表时间：
2020-04-21
期刊：
影响因子：
3.7
通讯作者：
Stodieck, Louis S.
中科院分区：
文献类型：
--
作者：
Smith, Rosamund C.;Cramer, Martin S.;Stodieck, Louis S.
众所周知，长时间太空飞行的微重力条件会导致骨骼肌萎缩，从而导致功能表现下降。为了评估抑制生长因子myostatin是否有可能逆转这些影响，在国际空间站饲养的小鼠接受了myostatin抗体治疗。在6周的研究中，地面对照组小鼠的握力比基准值增加了3.1%，而首次在太空中测量的握力显示，飞行动物的握力比基准值下降了7.8%。与地面对照组相比，太空中的对照组小鼠的DEXA测量肌肉质量增幅较小(分别为+3.9%和+5.6%)，尽管差异不显著。在研究结束时，所有被分析的个体飞行肢体肌肉(除EDL外)的重量都明显低于它们的地面对应肌肉(范围为-4.4%至-28.4%)。肌肉抑制素抗体YN41的治疗能够防止许多由空间引起的肌肉变化。YN41能够阻断航天飞行引起的肌肉握力下降，并能够显著增加飞行小鼠所有肌肉的重量(EDL除外)。YN41治疗的飞行小鼠的肌肉重量与地面免疫球蛋白小鼠的肌肉重量相同，但比目鱼肌除外，这表明有能力防止航天引起的萎缩。肌肉基因表达分析表明，微重力和肌肉生长抑素抑制对许多基因有显著影响。GAMT和Actc1基因的表达受到微重力和YN41相反方向的调控。抑制肌肉生长抑素不能克服微重力对股骨骨密度的显著降低，也不能增加地面对照组小鼠的股骨或椎骨骨密度。综上所述，肌肉抑制素抑制可能是微重力条件下骨骼肌有害后果的有效对策。
The microgravity conditions of prolonged spaceflight are known to result in skeletal muscle atrophy that leads to diminished functional performance. To assess if inhibition of the growth factor myostatin has potential to reverse these effects, mice were treated with a myostatin antibody while housed on the International Space Station. Grip strength of ground control mice increased 3.1% compared to baseline values over the 6 weeks of the study, whereas grip strength measured for the first time in space showed flight animals to be -7.8% decreased in strength compared to baseline values. Control mice in space exhibited, compared to ground-based controls, a smaller increase in DEXA-measured muscle mass (+3.9% vs +5.6% respectively) although the difference was not significant. All individual flight limb muscles analyzed (except for the EDL) weighed significantly less than their ground counterparts at the study end (range -4.4% to -28.4%). Treatment with myostatin antibody YN41 was able to prevent many of these space-induced muscle changes. YN41 was able to block the reduction in muscle grip strength caused by spaceflight and was able to significantly increase the weight of all muscles of flight mice (apart from the EDL). Muscles of YN41-treated flight mice weighed as much as muscles from Ground IgG mice, with the exception of the soleus, demonstrating the ability to prevent spaceflight-induced atrophy. Muscle gene expression analysis demonstrated significant effects of microgravity and myostatin inhibition on many genes. Gamt and Actc1 gene expression was modulated by microgravity and YN41 in opposing directions. Myostatin inhibition did not overcome the significant reduction of microgravity on femoral BMD nor did it increase femoral or vertebral BMD in ground control mice. In summary, myostatin inhibition may be an effective countermeasure to detrimental consequences of skeletal muscle under microgravity conditions.