The influence of passive stretch and NF-κB inhibitors on the morphology of dystrophic muscle fibers.
The influence of passive stretch and NF-κB inhibitors on the morphology of dystrophic muscle fibers.
复制标题
被动拉伸和NF-κB抑制剂对营养不良肌纤维形态的影响。
DOI：
10.1002/ar.21294
复制
发表时间：
2011-01
影响因子：
2
通讯作者：
Carlson, C. G.
中科院分区：
文献类型：
--
作者：
Siegel, A. S.;Henley, S.;Zimmerman, A.;Miles, M.;Plummer, R.;Kurz, J.;Balch, F.;Rhodes, J. A.;Shinn, G. L.;Carlson, C. G.
关键词：
胸骨三角肌（TS）是一种呼气肌肉，在吸气时被动伸展。被动拉伸的幅度取决于TS肌肉内单个纤维的位置，位于更尾部的纤维比头部区域中的纤维多拉伸约5%至10%。在肌营养不良症mdx小鼠模型中，TS表现出严重的病理学改变，通过NF-κB通路抑制剂治疗可改善。本研究的目的是评估体内被动牵张对非营养不良和mdx TS肌肉中纤维形态的影响，以及使用两种不同的NF-κB抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）和熊去氧胆酸（UDCA）治疗mdx小鼠的形态学益处。透射电子显微镜显示Z-线流，过度收缩，并在mdx纤维从基膜的质膜解离。在两个nondystrophic和mdx TS肌肉，纤维密度更大的尾部区域。与非营养不良TS相比，mdx TS中的纤维在所有区域的直径均大幅减少。PDTC或UDCA体内处理倾向于增加中间的纤维直径，减少尾部TS的纤维直径，同时减少中间区域的中央成核。这些结果表明，被动牵张诱导过度收缩和质膜异常的营养不良的肌肉，和被动牵张的幅度的差异可能会影响纤维形态和NF-κB抑制剂对营养不良形态的作用。
The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched approximately 5 to 10 % more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-κB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-κB inhibitors, pyrrolidine dithiocarbamate (PDTC) and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison to nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-κB inhibitors on dystrophic morphology.
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