Résumé :
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Duchenne muscular dystrophy (DMD) is a progressive disease, with patients gradually losing most of their skeletal muscle strength with increasing fibrosis and fatty tissue infiltration. Endomysial fibrosis is believed to be in part responsible of muscle weakness, since it is correlated to motor deficit. The mdx mouse also lacks dystrophin. From 3 weeks of age, time of a massive myofibre destruction, mdx skeletal muscle presents the same characteristics that DMD muscle including necrotic and regenerating myofibres, surrounded by inflammatory cells. However, excepted the diaphragm muscle that presents similar histology than DMD muscle, limb muscles do not present hallmark of fibrosis, excepted at very old age (at least 20 months). Moreover, adult mdx mouse does not present sign of muscle weakness (excepted after excentric exercise) while diaphragm presents dysfunction and loss of compliance. Our aim was to establish a fibrotic model of dystrophinopathy in adult - not ederly- mdx mouse by repeated mechanic microinjuries in hindlimb muscle. One week after the end of microinjuries, histological analysis and strength evaluation were performed. Histological stainings and collagene I immunolabellings showed the presence of endomysial fibrosis. Number of centrally nucleated myofibres was unchanged while the diameter of the fibres was decreased in treated muscle. Maximal force was decreased by more than 30% suggesting the involvement of endomysial fibrosis in muscle weakness. After one month resting, endomysial collagene I area was strongly decreased and force raised near control values, suggesting a fibrolytic process. The experimental model of skeletal muscle endomysial fibrosis we propose is transient, showing sequentially the establishment of fibrosis in the interstitial compartment, as it is observed in DMD, then a disappearance of this endomysial fibrosis. This model will be helpfull to study the cellular and molecular mechanisms involved in both fibrogenesis and fibrolysis processes in dystrophic skeletal muscle.
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