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首页> 外文期刊>Neuromuscular disorders: NMD >A novel quantitative morphometry approach to assess regeneration in dystrophic skeletal muscle
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A novel quantitative morphometry approach to assess regeneration in dystrophic skeletal muscle

机译：一种新的定量形态计量学方法，以评估营养不良性骨骼肌的再生

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摘要

Duchenne muscular dystrophy is an inherited degenerative muscle disease with progressive weakness of skeletal and cardiac muscle. Disturbed calcium homeostasis and signalling pathways result in degeneration/regeneration cycles with fibrotic remodelling of muscle tissue, sustained by chronic inflammation. In addition to altered microarchitecture, regeneration in dystrophic muscle fibres is often only classified by centrally located nuclei but correlation of the regeneration process to nuclear volumes, myosin amounts, architecture and functional quality are missing, in particular in old muscles where the regenerative capacity is exhausted. Such information could yield novel regeneration-to-function biomarkers. Here we used second harmonic generation and multi photon fluorescence microscopy in intact single muscle fibres from wild-type, dystrophic mdx and transgenic mdx mice expressing an δex 17-48 mini-dystrophin to determine the percentage of centronucleated fibres and nucleus-to-myosin volume ratio as a function of age. Based on this ratio we define a 'biomotoric efficiency' as an optical measure for fibre maturation, which is close to unity in adult wild-type and mini-dystrophin fibres, but smaller in very young and old mdx mice as a result of ongoing cell maturation (young) and regeneration (aged). With these parameters it is possible to provide a quantitative measure about muscle fibre regeneration.
机译：杜氏肌营养不良症是一种遗传性退行性肌肉疾病，骨骼肌和心肌进行性无力。钙稳态和信号通路的紊乱导致变性/再生循环，并由慢性炎症引起的肌肉组织纤维化重塑。除了改变的微结构外，营养不良性肌纤维的再生通常仅通过位于中心的细胞核进行分类，但是再生过程与核体积，肌球蛋白含量，结构和功能质量的相关性缺失，特别是在再生能力耗尽的旧肌肉中。这样的信息可以产生新颖的再生功能生物标记。在这里，我们对表达δex17-48微型肌营养不良蛋白的野生型，营养不良的mdx和转基因mdx小鼠的完整单条肌纤维使用了二次谐波产生和多光子荧光显微镜，以确定百日咳核纤维的百分比和核-肌球蛋白的体积比率与年龄的关系。基于该比率，我们将“生物运动效率”定义为纤维成熟的光学指标，在成年野生型和小型肌营养不良蛋白纤维中接近于统一性，但由于细胞持续不断，在非常年轻和年老的mdx小鼠中较小成熟（年轻）和再生（老化）。利用这些参数，可以提供有关肌肉纤维再生的定量测量。

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