Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury

Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury
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DOI:
10.1023/a:1014587918367
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发表时间:
2001-01-01
影响因子:
2.7
通讯作者:
Brooks, SV
Brooks, SV
中科院分区:
生物学3区
文献类型:
--
作者:
Dellorusso, C;Crawford, RW;Brooks, SV

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杜氏肌营养不良症(DMD)患者和mdx小鼠的骨骼肌缺乏肌营养不良蛋白,比对照组肌肉更容易受到收缩诱导的损伤。我们的目的是开发一种基于mdx小鼠肢体肌肉损伤的高敏感性的测定方法,用于评估治疗干预。该试验涉及两个伸展的最大激活胫骨前肌(TA)原位。相对于肌纤维长度的40%应变的拉伸从等长收缩的平台开始。一分钟后,通过等长收缩力的不足来评估损伤的程度。在所有年龄段(2-19个月),mdx小鼠肌肉的力量缺陷是对照组小鼠的4 - 7倍。对于对照组的肌肉,力缺陷与年龄无关,而在8个月大的mdx小鼠中,肌肉的力缺陷显著增加。老年mdx小鼠对肌肉损伤的敏感性增加并没有对肌肉质量或力量产生类似的不良影响。TA肌肉的原位拉伸协议提供了一个有价值的分析,在营养不良的肌肉损伤的机制的调查,并测试治疗干预逆转DMD。
Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) and mdx mice lack dystrophin and are more susceptible to contraction-induced injury than control muscles. Our purpose was to develop an assay based on the high susceptibility to injury of limb muscles in mdx mice for use in evaluating therapeutic interventions. The assay involved two stretches of maximally activated tibialis anterior (TA) muscles in situ. Stretches of 40% strain relative to muscle fiber length were initiated from the plateau of isometric contractions. The magnitude of damage was assessed one minute later by the deficit in isometric force. At all ages (2-19 months), force deficits were four- to seven-fold higher for muscles in mdx compared with control mice. For control muscles, force deficits were unrelated to age, whereas force deficits increased dramatically for muscles in mdx mice after 8 months of age. The increase in susceptibility to injury of muscles from older mdx mice did not parallel similar adverse effects on muscle mass or force production. The in situ stretch protocol of TA muscles provides a valuable assay for investigations of the mechanisms of injury in dystrophic muscle and to test therapeutic interventions for reversing DMD.