McCully K, Giger U, Argov Z, Valentine B, Cooper B, Chance B, Bank W
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104.
Muscle Nerve. 1991 Nov;14(11):1091-8. doi: 10.1002/mus.880141109.
Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.
杜兴氏肌肉营养不良症（DMD）是一种X连锁疾病，其特征为进行性肌肉无力和退化。肌营养不良蛋白是该疾病中缺失基因的产物。然而，营养不良过程的病因尚不清楚。肌肉运动后通常会出现短暂性肌肉损伤，这可能是肌肉生长和维持过程中的一个必要过程。因此，我们选择通过研究犬类X连锁动物模型（CXMD）来评估运动在杜兴氏肌营养不良症中的作用。这些犬类也缺乏肌营养不良蛋白，且具有与人类相似的临床症状。通过电刺激启动运动，并使用磷磁共振波谱（P-MRS）监测肌肉代谢。患有CXMD的犬类存在异常的肌肉病理学表现，血清肌酸激酶（CK）显著升高。与正常犬类相比，CXMD犬类在静息状态下无机磷酸盐（Pi）与磷酸肌酸（PCr）的比值升高（CXMD为0.166±0.054，正常犬类为0.073±0.017，均值±标准误）。静息状态下的三磷酸腺苷（ATP）、pH值、磷酸单酯（PME）和磷酸二酯（PDE）未见变化。CXMD犬类在刺激过程中的平均Pi/（Pi + PCr）和pH值正常。电刺激后两到三天，CXMD犬类的静息Pi/（Pi + PCr）比值显著升高（与0.172±0.054相比为0.127±0.029，均值±标准差）。正常犬类在刺激后Pi/（Pi + PCr）未升高。运动后，CXMD犬类血清CK的升高幅度比正常犬类大50倍。这些结果表明CXMD肌肉存在更严重的肌肉损伤，并提示在缺乏肌营养不良蛋白的情况下，运动诱导的肌肉损伤可能在营养不良过程中起作用。
