Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Compr Physiol. 2011 Jul;1(3):1353-63. doi: 10.1002/cphy.c100062.
The muscular dystrophies are a heterogeneous collection of progressive, inherited diseases of muscle weakness and degeneration. Although these diseases can vary widely in their etiology and presentation, nearly all muscular dystrophies cause exercise intolerance to some degree. Here, we focus on Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, as a paradigm for the effects of muscle disease on exercise capacity. First described in the mid-1800s, DMD is a rapidly progressive and lethal muscular dystrophy caused by mutations in the dystrophin gene. Dystrophin is a membrane-associated cytoskeletal protein, the loss of which causes numerous cellular defects including mechanical instability of the sarcolemma, increased influx of extracellular calcium, and cell signaling defects. Here, we discuss the physiological basis for exercise intolerance in DMD, focusing on the molecular and cellular defects caused by loss of dystrophin and how these manifest as organ-level dysfunction and reduced exercise capacity. The main focus of this article is the defects present in dystrophin-deficient striated muscle. However, discussion regarding the effects of dystrophin loss on other tissues, including vascular smooth muscle is also included. Collectively, the goal of this article is to summarize the current state of knowledge regarding the mechanistic basis for exercise intolerance in DMD, which may serve as an archetype for other muscular dystrophies and diseases of muscle wasting.
肌肉萎缩症是一组异质性的进行性遗传性肌肉无力和退化疾病。尽管这些疾病在病因和表现上可能有很大差异，但几乎所有的肌肉萎缩症都会在某种程度上导致运动不耐受。在这里，我们以杜氏肌营养不良症（DMD）为例，因为它是最常见的肌肉萎缩症形式，是肌肉疾病对运动能力影响的范例。DMD 于 19 世纪中期首次描述，是一种由 dystrophin 基因突变引起的快速进展性和致命性肌肉萎缩症。dystrophin 是一种膜相关的细胞骨架蛋白，其缺失会导致许多细胞缺陷，包括肌膜的机械不稳定性、细胞外钙内流增加和细胞信号缺陷。在这里，我们讨论了 DMD 运动不耐受的生理基础，重点讨论了缺失 dystrophin 引起的分子和细胞缺陷，以及这些缺陷如何表现为器官水平的功能障碍和运动能力下降。本文的主要重点是缺失 dystrophin 的横纹肌中存在的缺陷。然而，关于 dystrophin 缺失对包括血管平滑肌在内的其他组织的影响的讨论也包括在内。总的来说，本文的目的是总结目前关于 DMD 运动不耐受的机制基础的知识状况，这可能为其他肌肉萎缩症和肌肉消耗疾病提供范例。
