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目的 研究模拟失重对静息肌卫星细胞库及其增殖分化能力的影响。方法 采用尾悬吊法诱导小鼠失重性肌萎缩，采用–10º头低位卧床法诱导恒河猴失重性肌萎缩，利用实时荧光PCR、体外肌纤维培养组织免疫荧光双标记染色法，检测模拟失重环境对肌卫星细胞成肌调控因子的表达以及静息肌卫星细胞数量的影响。结果 模拟失重早期（尾悬吊3 d）引起小鼠骨骼肌内肌卫星细胞增殖期标记物Myf5和分化期标记物MyoD的mRNA表达一过性升高，尾悬吊第42天，除Myf5外，成肌调控因子Pax7、MyoD和myogenin的m RNA表达均受到抑制，静息期肌卫星细胞数量也明显下降；头低位卧床42 d显著抑制了恒河猴骨骼肌内成肌调控因子的表达。结论 啮齿类动物在模拟失重早期伴随一过性肌卫星细胞增殖分化能力的增强，提示损伤再生反应的发生；但中长期模拟失重刺激显著降低了啮齿类动物骨骼肌内pSmad3/Pax7双标记染色阳性静息肌卫星细胞的数目，并明显抑制了啮齿类和非人灵长类动物肌卫星细胞的增殖分化潜能。
Abstract：Objective To investigate the impact of simulated microgravity on the quiescent muscle satellite cell pool and its proliferative and differentiative capacity. Methods Tail suspension and-10° head-down tilt bedrest(HDBR) were used to induce microgravity-induced muscle atrophy in mice and rhesus macaques respectively. Real-time fluorescent PCR and in vitro myofiber culture with immunofluorescent double-labeling were used to assess changes in the expression of myogenic regulatory factors and the number of quiescent satellite cells under simulated microgravity. Results In the early phase of simulated microgravity(tail suspension for 3 days), mRNA expression of the proliferation marker Myf5 and the differentiation marker MyoD in murine skeletal muscle transiently increased. In mice subjected to tail suspension for 42 days, the mRNA expression of the myogenic regulatory factors Pax7, MyoD, and myogenin(excluding Myf5) was significantly suppressed, and the number of quiescent satellite cells was also markedly reduced. Concurrently, 42 days of HDBR significantly inhibited the expression of myogenic regulatory factors in the skeletal muscle of rhesus monkeys. Conclusion In rodents, early simulated microgravity triggers a transient enhancement in satellite cell proliferation and differentiation, indicating an acute regenerative response. However, prolonged exposure significantly reduces the population of pSmad3/Pax7 double-positive quiescent satellite cells in rodent skeletal muscle and markedly suppresses the proliferative and differentiative potential of satellite cells in both rodents and non-human primates.
[1]BACHMAN JF, CHAKKALAKAL JV. Satellite cells in the growth and maintenance of muscle[J]. Curr Top Dev Biol, 2024, 158:11-14.DOI:10.1016/bs.ctdb.2024.01.020.
[2]LIU D, BLACK BL, DERYNCK R. TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3[J]. Genes Dev, 2001, 15(22):2950-2966. DOI:10.1101/gad.925901.
[3]GE X, VAJJALA A, MCFARLANE C, et al. Lack of Smad3 signaling leads to impaired skeletal muscle regeneration[J]. Am J Physiol Endocrinol Metab, 2012, 303(1):E90-102. DOI:10.1152/ajpendo.00113.2012.
[4]ALOYSIUS A, DASGUPTA R, DHAWAN J. The transcription factor Lef1 switches partners from β-catenin to Smad3 during muscle stem cell quiescence[J]. Sci Signal, 2018, 11(540):eaan3000. DOI:10.1126/scisignal.aan3000.
[5]KOMAROVA MY, ROZHKOV SV, IVANOVA OA, et al. Cultured myoblasts derived from rat soleus muscle show altered regulation of proliferation and myogenesis during the course of mechanical unloading[J]. Int J Mol Sci, 2022, 23(16):9150. DOI:10.3390/ijms23169150.
[6]RADUGINA EA, ALMEIDA EAC, BLABER E, et al. Exposure to microgravity for 30 days onboard Bion M1 caused muscle atrophy and impaired regeneration in murine femoral Quadriceps[J]. Life Sci Space Res(Amst), 2018, 16:18-25. DOI:10.1016/j.lssr.2017.08.005.
[7]WANG XD, KAWANO F, MATSUOKA Y, et al. Mechanical load-dependent regulation of satellite cell and fiber size in rat soleus muscle[J]. Am J Physiol Cell Physiol, 2006, 290(4):C981-989. DOI:10.1152/ajpcell.00298.2005.
[8]OHIRA T, TERADA M, KAWANO F, et al. Region-specific responses of adductor longus muscle to gravitational load-dependent activity in Wistar Hannover rats[J]. PloS One, 2011, 6(6):e21044. DOI:10.1371/journal.pone.0021044.
[9]SANDONÀD, DESAPHY J-F, CAMERINO GM, et al. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission[J]. PloS One, 2012, 7(3):e33232. DOI:10.1371/journal.pone.0033232.
[10]HOSOYAMA T, ICHIDA S, KANNO M, et al. Microgravity influences maintenance of the human muscle stem/progenitor cell pool[J].Biochem Biophys Res Commun, 2017, 493(2):998-1003. DOI:10.1016/j.bbrc.2017.09.103.
[11]TAKAHASHI H, NAKAMURA A, SHIMIZU T. Simulated microgravity accelerates aging of human skeletal muscle myoblasts at the single cell level[J]. Biochem Biophys Res Commun, 2021, 578:115–121. DOI:10.1016/j.bbrc.2021.09.037.
[12]TARANTINO U, CARIATI I, MARINI M, et al. Effects of simulated microgravity on muscle stem cells activity[J]. Cell Physiol Biochem,2020, 54(4):736-747. DOI:10.33594/000000252.
[13]SWIDERSKI K, LYNCH GS. Murine models of Duchenne muscular dystrophy:is there a best model?[J]. Am J Physiol Cell Physiol, 2021,321(2):C409-C412. DOI:10.1152/ajpcell.00212.2021.
[14]SACCO A, MOURKIOTI F, TRAN R, et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice[J]. Cell, 2010, 143(7):1059-1071. DOI:10.1016/j.cell.2010.11.039.
[15]SOUSA-VICTOR P, GARCÍA-PRAT L, MUÑOZ-CÁNOVES P.Control of satellite cell function in muscle regeneration and its disruption in ageing[J]. Nat Rev Mol Cell Biol, 2022, 23(3):204-226. DOI:10.1038/s41580-021-00421-2.
基本信息:
DOI：10.16289/j.cnki.1002-0837.2026.02010
中图分类号:R852.22
引用信息:
[1]李文炯,袁敏,张鹏.模拟失重对骨骼肌卫星细胞库及其增殖分化潜能的影响[J].航天医学与医学工程,2026,37(02):173-177.DOI:10.16289/j.cnki.1002-0837.2026.02010.
基金信息:
载人航天工程航天医学实验领域项目（HYZHXM01017）
2026-04-25
2026-04-25