Abstract：
Dystrophin-deficient muscular dystrophy (Duchenne dystrophy) is characterized by impaired ion homeostasis, in which mitochondria play an important role. In the present work, using a model of dystrophin-deficient mdx mice, we revealed decrease in the efficiency of potassium ion transport and total content of this ion in the heart mitochondria. We evaluated the effect of chronic administration of the benzimidazole derivative NS1619, which is an activator of the large-conductance Ca2+-dependent K+ channel (mitoBKCa), on the structure and function of organelles and the state of the heart muscle. It was shown that NS1619 improves K+ transport and increases content of the ion in the heart mitochondria of mdx mice, but this is not associated with the changes in the level of mitoBKCa protein and expression of the gene encoding this protein. The effect of NS1619 was accompanied by the decrease in the intensity of oxidative stress, assessed by the level of lipid peroxidation products (MDA products), and normalization of the mitochondrial ultrastructure in the heart of mdx mice. In addition, we found positive changes in the tissue manifested by the decrease in the level of fibrosis in the heart of dystrophin-deficient animals treated with NS1619. It was noted that NS1619 had no significant effect on the structure and function of heart mitochondria in the wild-type animals. The paper discusses mechanisms of influence of NS1619 on the function of mouse heart mitochondria in Duchenne muscular dystrophy and prospects for applying this approach to correct pathology.
摘要：
肌营养不良蛋白缺乏型肌营养不良（Duchenne营养不良）的特征是离子稳态受损，其中线粒体起着重要作用。在目前的工作中,使用肌营养不良蛋白缺乏的mdx小鼠模型，我们发现钾离子转运效率和该离子在心脏线粒体中的总含量降低。我们评估了长期服用苯并咪唑衍生物NS1619的效果，该衍生物是大电导Ca2依赖性K通道（mitoBKCa）的激活剂，细胞器的结构和功能以及心肌的状态。研究表明，NS1619可以改善mdx小鼠心脏线粒体中的K转运并增加离子含量，但这与mitoBKCa蛋白水平的变化和编码该蛋白的基因表达无关。NS1619的效应伴随着氧化应激强度的降低，通过脂质过氧化产物(MDA产物)的水平评估，mdx小鼠心脏线粒体超微结构正常化。此外,我们发现,在接受NS1619治疗的肌营养不良蛋白缺陷型动物的心脏中,组织中的阳性变化表现为纤维化水平降低.值得注意的是，NS1619对野生型动物心脏线粒体的结构和功能没有显着影响。本文讨论了NS1619对Duchenne肌营养不良症小鼠心脏线粒体功能的影响机制，以及将这种方法用于纠正病理学的前景。
