Effects of botulinum toxin-induced paralysis on postnatal development of the supraspinatus muscle.

Effects of botulinum toxin-induced paralysis on postnatal development of the supraspinatus muscle.
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DOI:
10.1002/jor.21234
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发表时间:
2011-02
影响因子:
2.8
通讯作者:
Thomopoulos, Stavros
Thomopoulos, Stavros
中科院分区:
医学3区
文献类型:
--
作者:
Das, Rosalina;Rich, Jason;Kim, H. Mike;McAlinden, Audrey;Thomopoulos, Stavros

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力学环境在肌肉骨骼组织发育中起着重要作用。本研究的特点冈上肌肌肉的变化,由于在出生后的发展过程中去除机械线索。肌肉注射A型肉毒杆菌毒素(BTX)用于诱导和维持小鼠自出生以来的左肩瘫痪,而右肩接受盐水并用作对侧对照。另一组动物在没有任何注射的情况下正常发育。出生后在不同的时间点检查肌肉。与生理盐水组和正常组相比,BTX组中肌肉产生的最大等长强直力显著降低。瘫痪的肌肉较小,组织学评价显示明显的肌肉萎缩和脂肪堆积。在BTX组中,成肌基因myogenin、myoD 1、myf 5、myf 6和快II型肌球蛋白重链(MHC)亚型显著上调,而慢I型MHC亚型显著下调。BTX组C/EBPα、PPARγ2、leptin和lipoprotein lipase表达明显上调。结果表明,继发于BTX诱导的麻痹的肌肉负荷减少导致发育中的肌肉中的脂肪积累和肌肉变性。了解冈上肌发育过程中的分子和成分变化可能有助于识别和解决肩损伤(如新生儿臂丛神经麻痹)中发生的病理变化。
The mechanical environment plays an important role in musculoskeletal tissue development. The present study characterized changes in supraspinatus muscle due to removal of mechanical cues during postnatal development. An intramuscular injection of botulinum toxin type A (BTX) was used to induce and maintain paralysis in the left shoulders of mice since birth while the right shoulders received saline and served as contralateral controls. A separate group of animals was allowed to develop normally without any injections. Muscles were examined postnatally at various time points. The maximum isometric tetanic force generated by the muscle was significantly reduced in the BTX group compared to saline and normal groups. The paralyzed muscles were smaller and showed significant muscle atrophy and fat accumulation on histologic evaluation. Myogenic genes myogenin, myoD1, myf5, myf6 and fast type II myosin heavy chain (MHC) isoform were significantly upregulated while slow type I MHC isoform was significantly downregulated in the BTX group. Adipogenic genes C/EBPα, PPARγ2, leptin and lipoprotein lipase were significantly upregulated in the BTX group. Results indicate that reduced muscle loading secondary to BTX-induced paralysis leads to fat accumulation and muscle degeneration in the developing muscle. Understanding the molecular and compositional changes in developing supraspinatus muscles may be useful for identifying and addressing the pathological changes that occur in shoulder injuries such as neonatal brachial plexus palsy.
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