改变的肌肉转录组作为危急疾病幸存者的长期肌肉衰弱的分子基础
Ceren Uzun Ayar1, Fabian Güiza1,2, Inge Derese1
1Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Intensive care medicine
|June 10, 2025
概括
在重症监护室 (ICU) 入院后长期肌肉衰弱与肌肉RNA表达异常有关,表明线粒体功能受损和纤维化. 早期的亲肠道营养和葡萄糖皮质类药物可能有助于这些变化,提供预防的目标.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 密集护理医学 密集护理医学
背景情况:
- 危急病患者在重症监护室 (ICU) 住院多年后经常经历持续的肌肉衰弱,这严重影响了他们的生活质量.
- 这种长期肌肉衰弱的根本原因仍然不完全理解.
- 肌肉中的异常基因表达可能在持续的软弱中起作用,并有可能产生可修改的危险因素.
研究的目的:
- 研究前ICU患者肌肉中的长期RNA表达特征.
- 为了确定异常RNA表达是否与肌肉强度降低相关.
- 为了确定与异常RNA表达相关的潜在可修改的风险因素.
主要方法:
- 对EPaNIC试验的二次分析,涉及115名前ICU患者和30名对照.
- 肌肉转录组分析使用RNA测序5年后ICU.
- 路径过度表示,差异性共表达和多变量回归分析.
主要成果:
- 与对照人群相比,在前患者中确定了234个下调调节的RNA和116个上调调节的RNA.
- 检测到线粒体能量代谢受损,脂质代谢受损,纤维化增加.
- 异常的RNA表达与较低的肌肉强度相关;早期的肠胃营养和葡萄糖皮质体使用与改变的RNA表达有关.
结论:
- 关键疾病5年后肌肉RNA表达异常仍然存在,这表明线粒体功能障碍,脂质代谢改变和纤维化.
- 这些分子变化与长期肌肉力量的减少有关.
- 这些发现突出了可能可以避免的危险因素,并提出了预防和治疗ICU后肌肉衰弱的途径.
相关概念视频
01:13Formation of Muscle Fibers from Myoblasts
5.2K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
5.2K
01:21Satellite Stem Cells and Muscular Dystrophy
2.1K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
2.1K
01:28Disorders of the Skeletal Muscle
1.1K
The clinical conditions affecting the skeletal muscle tissue are broadly categorized as musculoskeletal and neuromuscular disorders.
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
1.1K