Cullen M J, Jaros E
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle-upon-Tyne, UK.
Acta Neuropathol. 1988;77(1):69-81. doi: 10.1007/BF00688245.
Ultrastructurally there are some clear differences in the pathology of muscle in X chromosome-linked muscular dystrophy of the mouse (mdx) and Duchenne muscular dystrophy (DMD). In particular the mouse muscle does not become infiltrated by large aggregations of connective tissue. It has been proposed that the differences are due to secondary biochemical changes consequent on the absence of dystrophin in both conditions. If this is the case, attention should be directed to the earliest ultrastructural changes held in common by both disorders. The most conspicuous of these, preceding myofibril breakdown, is dilation of the sarcoplasmic reticulum. Any physiological link between this and the absence of dystrophin remains to be determined. We suggest that in the mdx mouse, the widespread myofibre necrosis occurring at 3-4 weeks is triggered by increased mechanical demands causing the lack of dystrophin to become critical at this time. Subsequent regeneration of the myofibres appears to be almost completely successful. The ultimate failure of regeneration in DMD, in contrast, may be due to an additional factors acting in DMD exacerbating the lack of dystrophin. This additional factor may be associated with the plasma membrane lesions (not seen in mdx). Alternatively there may be factors present in the mouse that compensate for the lack of dystrophin. It is pointed out that to understand better the different processes occurring in mdx and DMD we need to learn more about the factors which control the balance between the growth of muscle and the growth of connective tissue in both normal and pathological human and mouse muscle.
在超微结构上，小鼠X染色体连锁型肌营养不良症（mdx）和杜兴氏肌营养不良症（DMD）的肌肉病理学存在一些明显差异。特别是小鼠肌肉不会被结缔组织的大量聚集所浸润。有人提出，这些差异是由于两种情况下缺乏抗肌萎缩蛋白导致的继发性生化变化。如果是这样，就应该关注这两种疾病共有的最早的超微结构变化。其中最明显的是在肌原纤维分解之前，肌浆网的扩张。这与抗肌萎缩蛋白缺失之间的任何生理联系仍有待确定。我们认为，在mdx小鼠中，3 - 4周时出现的广泛肌纤维坏死是由机械需求增加引发的，导致此时抗肌萎缩蛋白的缺乏变得至关重要。随后肌纤维的再生似乎几乎完全成功。相比之下，DMD中再生的最终失败可能是由于DMD中存在的其他因素加剧了抗肌萎缩蛋白的缺乏。这个额外因素可能与质膜损伤有关（mdx中未见到）。或者小鼠中可能存在补偿抗肌萎缩蛋白缺乏的因素。需要指出的是，为了更好地理解mdx和DMD中发生的不同过程，我们需要更多地了解在正常和病理状态下的人类和小鼠肌肉中控制肌肉生长和结缔组织生长之间平衡的因素。
