White Jason D, Davies Marilyn, McGeachie John, Grounds Miranda D
Department of Anatomy and Human Biology, University of Western Australia, Stirling Hwy, Western Australia, 6009, Crawley, Australia.
Neuromuscul Disord. 2002 Dec;12(10):909-16. doi: 10.1016/s0960-8966(02)00117-7.
The exogenous delivery of growth factors and cytokines is a potential therapeutic strategy to alleviate the degenerative effects of primary inherited myopathies such as Duchenne muscular dystrophy. The mdx mouse diaphragm is a model for examining the progressive degeneration of dystrophic muscle. We have delivered leukaemia inhibitory factor to the mdx diaphragm using slow release alginate gels. Previous studies have reported an improvement in the histology of mdx diaphragms after delivery of leukaemia inhibitory factor in a similar manner, but little attention has been paid to the mechanism by which leukaemia inhibitory factor acts. We have used autoradiography to examine cell proliferation, Evans Blue Dye to examine myofibre damage, and morphometric analysis to examine histology in leukaemia-inhibitory-factor-treated diaphragms and compared them with untreated mdx and normal C57Bl10/ScSn diaphragms. Autoradiography showed that although myoblast proliferation was significantly increased in leukaemia inhibitory factor-treated mdx diaphragms, leukaemia inhibitory factor did not reduce myofibre damage and no histological improvement was observed. The data presented here, while demonstrating a role for leukaemia inhibitory factor in myoblast proliferation, do not support a strong and consistent benefit of leukaemia inhibitory factor on dystrophic muscle in vivo as a means of alleviating the effects of chronic dystrophic muscle degeneration.
外源性递送生长因子和细胞因子是一种潜在的治疗策略，可减轻原发性遗传性肌病（如杜氏肌营养不良症）的退行性影响。mdx小鼠膈肌是研究营养不良性肌肉进行性退化的模型。我们使用缓释藻酸盐凝胶将白血病抑制因子递送至mdx小鼠的膈肌。此前的研究报道，以类似方式递送白血病抑制因子后，mdx膈肌的组织学有改善，但对白血病抑制因子的作用机制关注甚少。我们使用放射自显影术检测细胞增殖，伊文思蓝染料检测肌纤维损伤，并通过形态计量分析检测白血病抑制因子处理的膈肌的组织学，然后将其与未处理的mdx和正常C57Bl10/ScSn膈肌进行比较。放射自显影显示，虽然白血病抑制因子处理的mdx膈肌中肌母细胞增殖显著增加，但白血病抑制因子并未减少肌纤维损伤，也未观察到组织学改善。本文给出的数据虽然证明了白血病抑制因子在肌母细胞增殖中的作用，但并不支持白血病抑制因子作为减轻慢性营养不良性肌肉退化影响的手段在体内对营养不良性肌肉有强大且持续的益处。
