Krupnick Alexander S, Zhu Jianliang, Nguyen Taitan, Kreisel Daniel, Balsara Keki R, Lankford Edward B, Clark Charles C, Levine Sanford, Stedman Hansell H, Shrager Joseph B
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
J Appl Physiol (1985). 2003 Feb;94(2):411-9. doi: 10.1152/japplphysiol.00689.2002.
Since the finding that the mdx mouse diaphragm, in contrast to limb muscles, undergoes progressive degeneration analogous to that seen in Duchenne muscular dystrophy, the relationship between the workload on a muscle and the pathogenesis of dystrophy has remained controversial. We increased the work performed by the mdx mouse diaphragm in vivo by tracheal banding and evaluated the progression of dystrophic changes in that muscle. Despite the establishment of dramatically increased respiratory workload and accelerated myofiber damage documented by Evans blue dye, no change in the pace of progression of dystrophy was seen in banded animals vs. unbanded, sham-operated controls. At the completion of the study, more centrally nucleated fibers were evident in the diaphragms of banded mdx mice than in sham-operated mdx controls, indicating that myofiber regeneration increases to meet the demands of the work-induced damage. These data suggest that there is untapped regenerative capacity in dystrophin-deficient muscle and validates experimental efforts aimed at augmenting regeneration within skeletal muscle as a therapeutic strategy in the treatment of dystrophinopathies.
自从发现mdx小鼠的膈肌与肢体肌肉不同，会发生类似于杜氏肌营养不良症中所见的进行性退化以来，肌肉的工作量与营养不良症发病机制之间的关系一直存在争议。我们通过气管结扎增加了mdx小鼠膈肌在体内的工作量，并评估了该肌肉中营养不良性变化的进展。尽管通过伊文思蓝染料记录到呼吸工作量显著增加且肌纤维损伤加速，但与未结扎的假手术对照相比，结扎动物的营养不良进展速度没有变化。在研究结束时，结扎的mdx小鼠膈肌中比假手术的mdx对照有更多的中央核纤维，这表明肌纤维再生增加以满足工作诱导损伤的需求。这些数据表明，肌营养不良蛋白缺乏的肌肉中存在未被开发的再生能力，并验证了旨在增强骨骼肌再生作为治疗肌营养不良症治疗策略的实验努力。
