Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Neurosci Res. 2012 Feb;72(2):181-6. doi: 10.1016/j.neures.2011.10.005. Epub 2011 Oct 21.
Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy. We demonstrated that poloxamer 188 (P188), a membrane sealant, is effective in reducing the loss of muscle mass in SJL mice when administered using an osmotic pump for 6 weeks. We did not observe significant changes over a 2-week administration period, suggesting that longthier observation is necessary to determine the effectiveness of P188. We also examined exercise endurance in P188-administered SJL mice using a rolling cage. Phosphorylated p38 was found to be reduced in P188-administered SJL mice; additionally, using microarray analysis, we found diminished expression of atrogin-1, an E3 ubiquitin ligase, as the effector of muscular atrophy. Chronic infusion of P188 to dysferlin-deficient SJL mice reduced muscular atrophy, and administering p38 and atrogin-1 in the gastrocnemius muscle improved its motor function. These results provide a basis for potential treatments for dysferlin-deficient skeletal muscle fibers.
肌营养不良蛋白缺乏的 SJL 小鼠常用于研究肌营养不良症。我们证明，泊洛沙姆 188（P188），一种膜密封剂，在通过渗透泵给药 6 周时，可有效减少 SJL 小鼠的肌肉质量损失。我们在给药 2 周内没有观察到明显变化，这表明需要更长时间的观察来确定 P188 的有效性。我们还使用滚动笼检查了 P188 给药的 SJL 小鼠的运动耐力。发现在 P188 给药的 SJL 小鼠中磷酸化的 p38 减少；此外，通过微阵列分析，我们发现作为肌肉萎缩效应物的 E3 泛素连接酶 atrogin-1 的表达减少。慢性输注 P188 可减少肌营养不良蛋白缺乏的 SJL 小鼠的肌肉萎缩，并且在比目鱼肌中给予 p38 和 atrogin-1 可改善其运动功能。这些结果为治疗肌营养不良蛋白缺乏的骨骼肌纤维提供了基础。
