Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment
Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment
复制标题
DOI：
10.1152/ajpgi.00314.2013
复制
发表时间：
2014-02-01
影响因子：
4.5
通讯作者：
Nouailhetas, Viviane L. A.
中科院分区：
文献类型：
--
作者：
Alves, Gabriel A.;Silva, Luisa R.;Nouailhetas, Viviane L. A.
蛋白质肌营养不良蛋白是肌营养不良蛋白相关蛋白复合物的组分，其将收缩机制连接到质膜和细胞外基质。它的缺乏导致一种称为杜氏肌营养不良症（DMD）的疾病，这种疾病的特征是进行性骨骼肌变性，运动残疾和早期死亡。在最常见的DMD动物模型mdx小鼠中，观察到肌肉细胞损失，但总体疾病变化不如DMD患者严重。DMD患者和mdx小鼠胃肠道组织的变化尚未完全了解。因此，我们研究了形态学（光学和电子显微镜）和收缩功能（通过记录等长收缩反应）与mdx小鼠回肠中Ca2+处理改变之间的可能关系。我们证明了回肠肌层厚度减少27%，粘膜层部分受损，肠肌细胞线粒体部分受损。在功能上，来自mdx的回肠在拉伸过程中呈现出增强的反应性，与改变的钙内流诱导的收缩相关的机电和药物力学信号的轻度损伤，与对照动物相比，肌浆网Ca2+储存没有改变（维持咖啡因和毒胡萝卜素诱导的收缩）。因此，这表明，蛋白质dystrophin在小鼠肠道的微观结构和超微结构的保护中起着重要的作用，而发挥一个小的，但重要的作用，涉及肠收缩反应和钙处理。
Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extra-cellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. In mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in DMD patients. Alterations in gastrointestinal tissues from DMD patients and mdx mice are not yet completely understood. Thus, we investigated the possible relationships between morphological (light and electron microscopy) and contractile function (by recording the isometric contractile response) with alterations in Ca2+ handling in the ileum of mdx mice. We evidenced a 27% reduction in the ileal muscular layer thickness, a partial damage to the mucosal layer, and a partial damage to mitochondria of the intestinal myocytes. Functionally, the ileum from mdx presented an enhanced responsiveness during stretch, a mild impairment in both the electromechanical and pharmacomechanical signaling associated with altered calcium influxinduced contraction, with no alterations in the sarcoplasmic reticulum Ca2+ storage (maintenance of the caffeine and thapsigargin-induced contraction) compared with control animals. Thus, it is evidenced that the protein dystrophin plays an important role in the preservation of both the microstructure and ultrastructure of mice intestine, while exerting a minor but important role concerning the intestinal contractile responsiveness and calcium handling.