Abstract:

Objective  To observe the skeletal muscle dystrophin expression and neuromuscular junction (NMJ) morphology in adult and young mdx mice.  Methods  Select eight 8-week-old specific pathogen free (SPF) C57BL/6 mice, four 8-week-old adult mdx mice and four 2-week-old young mdx mice. Observe the histological features of myoctyes by HE staining, and detect the expression changes of gastrocnemius muscle dystrophin and morphology of NMJ by immunofluorescent staining.  Results  The gastrocnemius muscle cells of C57BL/6 mice were almost uniform in size and polygonal. The nuclei were located in the peripheral of cells, while only a few were located in the center of myofiber. The sarcolemma expressed dystrophin uniformly and NMJ were intact. The gastrocnemius muscle cells of mdx mice were not consistent in size and had round shape. Part of nuclei were centralized. Only a few muscle cells expressed dystrophin. The acetylcholine receptor (AChR) on postsynaptic membrane of adult mdx mice were broken into small fragments, and the nerve terminal of presynaptic membrane had a great increase in the number of attenuated neurites. The morphology of NMJ in young mdx mice was similar to C57BL/6 mice. In both adult and young mdx mice, the number of NMJ had a great reduction, the cross-sectional area of presynaptic and postsynaptic membrane decreased obviously, and intercellular neural axons were thinned evidently. Conclusions  The absence of dystrophin in mdx mice is not the direct factor causing NMJ abnormities. The degeneration of muscle in the development of DMD may lead to the changes.

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摘要：

目的 观察Duchenne 型肌营养不良症模型小鼠骨骼肌肌膜抗肌萎缩蛋白（dystrophin）表达变化和神经肌肉接头形态，分析其可能机制。方法 C57BL/6 和mdx 小鼠各8 只，HE 染色观察肌细胞组织学形态，免疫荧光染色检测腓肠肌肌膜dystrophin 蛋白表达变化和神经肌肉接头形态。结果 C57BL/6 小鼠腓肠肌肌细胞大小基本一致，呈多角形，胞核位于细胞周边、极少数位于肌纤维中心；肌膜均匀表达dystrophin 蛋白；神经肌肉接头形态完好。Mdx 小鼠腓肠肌肌细胞大小不一致，呈圆形，部分胞核趋中心化；仅少量或个别肌细胞表达dystrophin 蛋白；mdx 种鼠突触后膜乙酰胆碱受体断裂成小片段，突触前膜神经末梢突起增多、变细，而mdx幼鼠神经肌肉接头形态与C57BL/6 小鼠基本一致；mdx小鼠神经肌肉接头数目明显减少，突触前膜和突触后膜横截面积明显减小，肌细胞间神经轴突明显变细。结论 Mdx 小鼠骨骼肌肌膜dystrophin 蛋白缺失并非导致神经肌肉接头改变的直接因素，可能与病情进展有关。

关键词: 肌营养不良, 杜氏, 肌营养不良蛋白, 神经肌肉接头, 疾病模型, 动物