Administration of insulin-like growth factor-I improves fatigue resistance of skeletal muscles from dystrophic mdx mice
Administration of insulin-like growth factor-I improves fatigue resistance of skeletal muscles from dystrophic mdx mice
复制标题
DOI：
10.1002/mus.20082
复制
发表时间：
2004-09-01
期刊：
影响因子：
3.4
通讯作者：
Lynch, GS
中科院分区：
文献类型：
--
作者：
Gregorevic, P;Plant, DR;Lynch, GS
肌肉疲劳发生在许多神经肌肉疾病中，包括肌营养不良症，并且它导致受影响患者的功能能力丧失和生活质量降低。在给予胰岛素样生长因子-I（IGF-I）后，在mdx小鼠的膈肌中观察到抗疲劳性的改善。类似的治疗是否能改善mdx小鼠的运动肌肉功能尚不清楚。我们检查了IGF-I给药（每天lmg/kg s.c.持续8周）对mdx小鼠趾长伸肌（EDL）和比目鱼肌的结构、代谢和功能特性的影响，并测试IGF-I治疗将改善这些肌肉功能的假设。治疗后，肌肉在重复最大收缩过程中比未治疗小鼠的肌肉更耐疲劳，这一改善与在细胞（单纤维）收缩激活特征没有变化的情况下肌纤维琥珀酸脱氢酶活性增加有关。这些发现具有重要的临床意义，不仅适用于肌营养不良症，而且适用于所有神经肌肉病理学，其中运动肌肉的疲劳限制了功能能力并降低了生活质量。
Muscle fatigue occurs in many neuromuscular diseases, including the muscular dystrophies, and it contributes to a loss of functional capacity and reduced quality of life for affected patients. An improvement in fatigue resistance has been observed in diaphragm muscles of mdx mice following insulin-like growth factor-I (IGF-I) administration. Whether similar treatment can improve locomotor muscle function in mdx mice is not known. We examined the efficacy of IGF-I administration (1 mg/kg daily s.c. for 8 weeks) on structural, metabolic, and functional properties of extensor digitorum longus (EDL) and soleus muscles of mdx mice, and tested the hypothesis that IGF-I treatment would improve, function in these muscles. After treatment, muscles were more resistant to fatigue during repeated maximal contractions than muscles from untreated mice, an improvement associated with increased muscle fiber succinate dehydrogenase activity in the absence of changes in cellular (single-fiber) contractile activation characteristics. The findings have important clinical implications, not just for the dystrophinopathies, but for all neuromuscular pathologies where fatigue of locomotor muscles limits functional capacity and decreases quality of life.