Keeling Richard M, Golumbek Paul T, Streif Elizabeth M, Connolly Anne M
Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Muscle Nerve. 2007 Jan;35(1):43-8. doi: 10.1002/mus.20646.
Although corticosteroids alleviate weakness in mdx mice, no long-term treatment has determined whether this benefit is maintained. We studied mdx mice forelimb grip strength and fatigue from 3 through 84 weeks and followed survival through 104 weeks. The mdx mice were given twice weekly oral prednisolone (5 mg/kg) beginning at 3 or 4 weeks. Treated mdx mice survived longer than untreated mice. Between 3 and 10 weeks, treated and untreated mdx mice had similar strength. Between 10 and 24 weeks, strength and strength per gram body weight declined more slowly in treated than untreated mdx mice. Between 24 and 84 weeks, treated and untreated mdx mice declined in strength at the same rate, although treated mice remained stronger. Forelimb grip fatigue was present in untreated mdx mice at all time-points compared to wild-type and was not changed significantly by treatment. We have demonstrated long-term benefit of oral prednisolone in the mdx mouse model of Duchenne muscular dystrophy (DMD). As corticosteroids remain the most validated long-term treatment of DMD, this work may allow for better prediction of synergistic treatments likely to translate to effective improvement for boys with this progressive muscular dystrophy.
尽管皮质类固醇可减轻mdx小鼠的肌无力，但尚无长期治疗来确定这种益处是否能持续。我们研究了mdx小鼠从3周到84周的前肢握力和疲劳情况，并追踪其至104周的生存期。mdx小鼠在3或4周龄时开始每周两次口服泼尼松龙（5 mg/kg）。接受治疗的mdx小鼠比未治疗的小鼠存活时间更长。在3至10周之间，接受治疗和未接受治疗的mdx小鼠力量相似。在10至24周之间，接受治疗的mdx小鼠力量和每克体重的力量下降速度比未治疗的小鼠更慢。在24至84周之间，接受治疗和未接受治疗的mdx小鼠力量下降速度相同，尽管接受治疗的小鼠仍然更强壮。与野生型相比，未治疗的mdx小鼠在所有时间点均存在前肢握力疲劳，且治疗对此无明显改变。我们已经证明口服泼尼松龙在杜兴氏肌营养不良症（DMD）的mdx小鼠模型中具有长期益处。由于皮质类固醇仍然是DMD最有效的长期治疗方法，这项工作可能有助于更好地预测协同治疗方法，这些方法可能会有效改善患有这种进行性肌营养不良症的男孩的病情。
