Baati Narjes, Mougenot Nathalie, Lemaitre Mégane, Kirsch Marine, Agbulut Onnik, Ferry Arnaud, Vitiello Damien
Institute of Sport and Health Sciences of Paris - URP3625, Université de Paris, Paris, France.
Sorbonne Universités, PECMV, Paris, France.
Intractable Rare Dis Res. 2021 Nov;10(4):269-275. doi: 10.5582/irdr.2021.01097.
Duchenne muscular dystrophy (DMD) is a recessive hereditary myopathy due to deficiency of functional dystrophin. Current therapeutic interventions need more investigation to slow down the progression of skeletal and cardiac muscle weakness. In humans, there is a lack of an adapted training program. In animals, the murine model with a background (D2-) was recently suggested to present pathological features closer to that of humans. In this study, we characterized skeletal and cardiac muscle functions in males and females D2- mice compared to control groups. We also evaluated the impact of high intensity interval training (HIIT) in these muscles in females and males. HIIT was performed 5 times per week during a month on a motorized treadmill. Specific maximal isometric force production and weakness were measured in the muscle (TA). Sedentary male and female D2- mice produced lower absolute and specific maximal force compared to control mice. Dystrophic mice showed a decline of force generation during repetitive stimulation compared to controls. This reduction was greater for male D2- mice than females. Furthermore, trained D2- males showed an improvement in force generation after the fifth lengthening contraction compared to sedentary D2- males. Moreover, echocardiography measures revealed a decrease in left ventricular end-diastolic volume, left ventricular ejection volume and left ventricular end-diastolic diameter in sedentary male and female D2- mice. Overall, our results showed a serious muscle function alteration in female and male D2- mice compared to controls. HIIT may delay force loss especially in male D2- mice.
杜氏肌营养不良症（DMD）是一种由于功能性肌营养不良蛋白缺乏导致的隐性遗传性肌病。目前的治疗干预措施需要更多研究来减缓骨骼肌和心肌无力的进展。在人类中，缺乏合适的训练方案。在动物方面，最近有人提出具有特定背景（D2-）的小鼠模型呈现出更接近人类的病理特征。在本研究中，我们对雄性和雌性D2-小鼠与对照组相比的骨骼肌和心肌功能进行了特征描述。我们还评估了高强度间歇训练（HIIT）对这些小鼠雌雄两性肌肉的影响。HIIT在电动跑步机上每周进行5次，持续一个月。在胫骨前肌（TA）中测量特定的最大等长力产生和肌力减弱情况。与对照小鼠相比，久坐不动的雄性和雌性D2-小鼠产生的绝对和特定最大力量较低。与对照组相比，营养不良的小鼠在重复刺激期间力的产生有所下降。雄性D2-小鼠的这种下降比雌性更大。此外，与久坐不动的D2-雄性小鼠相比，经过训练的D2-雄性小鼠在第五次延长收缩后力的产生有所改善。此外，超声心动图测量显示，久坐不动的雄性和雌性D2-小鼠的左心室舒张末期容积、左心室射血容积和左心室舒张末期直径均减小。总体而言，我们的结果表明，与对照组相比，雄性和雌性D2-小鼠存在严重的肌肉功能改变。HIIT可能会延缓力的丧失，尤其是在雄性D2-小鼠中。
