Austin L, Bower J J, Bennett T M, Lynch G S, Kapsa R, White J D, Barnard W, Gregorevic P, Byrne E
Melbourne Neuromuscular Research Institute, St. Vincent's Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia.
Muscle Nerve. 2000 Nov;23(11):1700-5. doi: 10.1002/1097-4598(200011)23:11<1700::aid-mus5>3.0.co;2-w.
Although the muscles of the mdx mouse lack dystrophin, the protein absent in muscles of humans affected with Duchenne muscular dystrophy (DMD), the only mdx muscle to degenerate in a manner similar to those of DMD boys is the diaphragm. We have previously shown that leukemia inhibitory factor (LIF) is a trauma factor that enhances muscle repair in vivo and, when applied exogenously, increases the fiber size of mdx skeletal muscle. Furthermore, we developed a controlled release device for LIF based on a calcium alginate rod (release rate about 0.5% per day). These rods were sutured to the abdominal surface of the hemidiaphragm of mdx mice 3 months old. At age 6 months the mice were killed and the diaphragm muscles fixed and sectioned. The sections showed obvious muscle degeneration at 3 months of age in mdx mouse diaphragms and further degeneration at 6 months in saline-perfused muscle. Hemidiaphragm muscles continuously exposed to LIF over the same period contained more normal myofibers, larger regenerated fibers, and less adipose tissue and other non-contractile tissue. Morphometric analysis of the diaphragm sections was carried out. The LIF-treated animals showed a significant increase in fiber number and size compared to saline rod controls. The amount of nonmuscle (connective tissue and adipose tissue) was significantly reduced and the maximum force-producing capacity of isolated diaphragm muscle strips was higher in LIF-treated mice. The results demonstrate that LIF treatment ameliorates the dystrophic abnormalities in mdx mouse diaphragm.
尽管mdx小鼠的肌肉缺乏抗肌萎缩蛋白（杜兴氏肌营养不良症（DMD）患者肌肉中缺失的蛋白质），但mdx小鼠中唯一以与DMD男孩肌肉相似方式退化的肌肉是膈肌。我们之前已经表明，白血病抑制因子（LIF）是一种创伤因子，可在体内增强肌肉修复，并且在外部应用时可增加mdx小鼠骨骼肌的纤维大小。此外，我们基于海藻酸钙棒开发了一种LIF控释装置（释放速率约为每天0.5%）。将这些棒缝合到3月龄mdx小鼠半膈肌的腹面。在6月龄时处死小鼠，固定并切片膈肌肌肉。切片显示，mdx小鼠膈肌在3月龄时出现明显的肌肉退化，而在生理盐水灌注的肌肉中，6月龄时退化进一步加剧。在同一时期持续暴露于LIF的半膈肌含有更多正常肌纤维、更大的再生纤维，以及更少的脂肪组织和其他非收缩性组织。对膈肌切片进行了形态计量分析。与生理盐水棒对照组相比，接受LIF治疗的动物的纤维数量和大小显著增加。非肌肉组织（结缔组织和脂肪组织）的量显著减少，并且在接受LIF治疗的小鼠中，分离的膈肌肌肉条的最大产力能力更高。结果表明，LIF治疗可改善mdx小鼠膈肌的营养不良异常。
