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脊髓损伤患者电刺激运动的基因组学和表观基因组学评估:精准康复应用。

Genomic and Epigenomic Evaluation of Electrically Induced Exercise in People With Spinal Cord Injury: Application to Precision Rehabilitation.

机构信息

Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.

Department of Biochemistry, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.

出版信息

Phys Ther. 2022 Jan 1;102(1). doi: 10.1093/ptj/pzab243.

DOI:10.1093/ptj/pzab243
PMID:34718779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8754383/
Abstract

OBJECTIVE

Physical therapists develop patient-centered exercise prescriptions to help overcome the physical, emotional, psychosocial, and environmental stressors that undermine a person's health. Optimally prescribing muscle activity for people with disability, such as a spinal cord injury, is challenging because of their loss of volitional movement control and the deterioration of their underlying skeletal systems. This report summarizes spinal cord injury-specific factors that should be considered in patient-centered, precision prescription of muscle activity for people with spinal cord injury. This report also presents a muscle genomic and epigenomic analysis to examine the regulation of the proliferator-activated receptor γ coactivator 1α (PGC-1α) (oxidative) and myostatin (hypertrophy) signaling pathways in skeletal muscle during low-frequency (lower-force) electrically induced exercise versus higher-frequency (higher-force) electrically induced exercise under constant muscle recruitment (intensity).

METHODS

Seventeen people with spinal cord injury participated in 1 or more unilateral electrically induced exercise sessions using a lower-force (1-, 3-, or 5-Hz) or higher-force (20-Hz) protocol. Three hours after the exercise session, percutaneous muscle biopsies were performed on exercised and nonexercised muscles for genomic and epigenomic analysis.

RESULTS

We found that low-frequency (low-force) electrically induced exercise significantly increased the expression of PGC-1α and decreased the expression of myostatin, consistent with the expression changes observed with high-frequency (higher-force) electrically induced exercise. Further, we found that low-frequency (lower-force) electrically induced exercise significantly demethylated, or epigenetically promoted, the PGC-1α signaling pathway. A global epigenetic analysis showed that >70 pathways were regulated with low-frequency (lower-force) electrically induced exercise.

CONCLUSION

These novel results support the notion that low-frequency (low-force) electrically induced exercise may offer a more precise rehabilitation strategy for people with chronic paralysis and severe osteoporosis. Future clinical trials are warranted to explore whether low-frequency (lower-force) electrically induced exercise training affects the overall health of people with chronic spinal cord injury.

摘要

目的

物理治疗师制定以患者为中心的运动处方,以帮助克服身体、情感、心理社会和环境压力,这些压力会破坏人的健康。为患有残疾(如脊髓损伤)的人最佳地开具肌肉活动处方是具有挑战性的,因为他们失去了自主运动控制能力,并且其潜在的骨骼系统也在恶化。本报告总结了与脊髓损伤相关的因素,这些因素在为脊髓损伤患者制定以患者为中心的、精准的肌肉活动处方时应加以考虑。本报告还介绍了一项肌肉基因组和表观基因组分析,以检查低频(低力)电诱导运动与高频(高力)电诱导运动在恒定肌肉募集(强度)下对骨骼肌中过氧化物酶体增殖物激活受体 γ 共激活因子 1α(PGC-1α)(氧化)和肌肉生长抑制素(肥大)信号通路的调节。

方法

17 名脊髓损伤患者参加了 1 次或多次单侧电诱导运动,使用低力(1、3 或 5 Hz)或强力(20 Hz)方案。运动后 3 小时,对运动和非运动肌肉进行经皮肌肉活检,进行基因组和表观基因组分析。

结果

我们发现低频(低力)电诱导运动显著增加了 PGC-1α 的表达,降低了肌肉生长抑制素的表达,与高频(高力)电诱导运动观察到的表达变化一致。此外,我们发现低频(低力)电诱导运动显著去甲基化或表观遗传促进了 PGC-1α 信号通路。全面的表观基因组分析显示,低频(低力)电诱导运动调节了 >70 条通路。

结论

这些新的结果支持低频(低力)电诱导运动可能为慢性瘫痪和严重骨质疏松症患者提供更精确的康复策略的观点。需要进行未来的临床试验来探讨低频(低力)电诱导运动训练是否会影响慢性脊髓损伤患者的整体健康。

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