Horowits R, Dalakas M C, Podolsky R J
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Ann Neurol. 1990 Jun;27(6):636-41. doi: 10.1002/ana.410270609.
We measured the intrinsic mechanical properties and protein content of single skinned muscle fibers obtained from patients who had Duchenne muscular dystrophy. To check for possible nonspecific changes caused by muscle disease per se, we also studied the properties of muscle fibers obtained from patients exhibiting severe muscle weakness due to polymyositis. Relative to control fibers obtained from 4 patients with normal or nonmyopathic muscle, we found no significant changes in the ability of muscle fibers from the patients with Duchenne muscular dystrophy or polymyositis to generate active tension in response to calcium or resting tension in response to stretch. In addition, we found no significant changes in the concentrations of the major contractile proteins myosin and actin, of the elastic protein titin, or of the structural proteins nebulin and alpha-actinin. In contrast, immunocytochemical studies showed that dystrophin was absent in the biopsy specimens from the patients with Duchenne muscular dystrophy, but localized at the cell membrane in all of the other muscle biopsy specimens used in this study. These results indicate that myofibrils assemble and function normally in Duchenne muscular dystrophy. Therefore, the absence of dystrophin, which is the primary biochemical defect in this disease, leads to clinical weakness by causing the breakdown of muscle fibers that were once capable of generating normal force, while the surviving fibers exhibit normal contractility.
我们测量了从患有杜兴氏肌营养不良症的患者身上获取的单根去表皮肌纤维的内在力学特性和蛋白质含量。为了检查肌肉疾病本身可能引起的非特异性变化，我们还研究了因多发性肌炎而出现严重肌肉无力的患者的肌纤维特性。相对于从4名肌肉正常或无肌病的患者身上获取的对照纤维，我们发现，杜兴氏肌营养不良症或多发性肌炎患者的肌纤维在对钙产生主动张力或对拉伸产生静息张力方面的能力没有显著变化。此外，我们发现主要收缩蛋白肌球蛋白和肌动蛋白、弹性蛋白肌联蛋白以及结构蛋白伴肌动蛋白和α - 辅肌动蛋白的浓度没有显著变化。相比之下，免疫细胞化学研究表明，杜兴氏肌营养不良症患者的活检标本中不存在肌营养不良蛋白，但在本研究中使用的所有其他肌肉活检标本中，肌营养不良蛋白定位于细胞膜。这些结果表明，在杜兴氏肌营养不良症中，肌原纤维组装和功能正常。因此，作为该疾病主要生化缺陷的肌营养不良蛋白的缺失，通过导致曾经能够产生正常力量的肌纤维分解而导致临床肌无力，而存活的纤维表现出正常的收缩性。
