4-氨基吡啶可减轻小鼠坐骨神经挤压损伤后的肌肉萎缩。
4-Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice.
机构信息
Department of Orthopaedics, The Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
Department of Orthopaedics and Rehabilitation, Center for Orthopaedics and Translational Science, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Mail Code H089, Hershey, Pennsylvania, 17033, USA.
出版信息
Muscle Nerve. 2019 Aug;60(2):192-201. doi: 10.1002/mus.26516. Epub 2019 May 30.
INTRODUCTION
We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown.
METHODS
Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed.
RESULTS
In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells.
DISCUSSION
These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.
简介
我们最近证明了 4-氨基吡啶（4-AP），一种钾通道阻滞剂，在增强坐骨神经挤压损伤后小鼠的髓鞘再生和神经传导速度以及运动功能恢复方面的有益作用。尽管神经损伤后肌肉萎缩非常迅速，但 4-AP 对肌肉萎缩和内在肌肉收缩功能的影响在很大程度上是未知的。
方法
将小鼠分为坐骨神经挤压损伤组和无损伤组，并在 3、7 和 14 天内用/不用 4-AP 或生理盐水处理，以评估骨骼肌的形态、功能和转录特性。
结果
除了改善体内功能外，4-AP 还显著减少了肌肉萎缩，增加了肌纤维直径和收缩力。肌肉萎缩的减少与萎缩相关基因表达的减弱和增殖干细胞表达的增加有关。
讨论
这些发现为 4-AP 对抗神经损伤引起的肌肉萎缩和功能障碍的潜在治疗益处提供了新的见解。肌肉神经 60: 192-201, 2019.
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