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首页> 外文期刊>Journal of Cellular Physiology >Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy
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Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy

机译：途径与他达拉非的改进杜氏肌萎缩症

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Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray-based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up-regulation of PGC-1; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z-disk. J. Cell. Physiol. 230: 224-232, 2016. (c) 2015 Wiley Periodicals, Inc.
机译：无数为杜乡和治疗方法贝克肌营养不良(DMD和BMD),最多常见的x连锁肌肉退行性疾病被提出。明显是使用有益的影响糖皮质激素。改善营养不良的心脏和骨骼肌肉的持续cGMP水平二次阻塞的退化磷酸二酯酶5 (PDE5)。我们进行了一项研究调查的影响具体PDE5抑制剂、他达拉非营养不良的骨骼肌功能。与他达拉非药物治疗在mdx老鼠。生理测试,以及组织学生化分析,证实的疗效的治疗。基因组分析评估基因的模式表情肌肉样品中得到的不同组的动物对待他达拉非。几类调制基因。表明PDE5抑制可以改善营养不良的各级代理。他达拉非会导致(1)增加脂质新陈代谢;纤维由PGC-1上调;增加蛋白质合成效率;在Z-disk更好的肌动蛋白网络组织。细胞。期刊、公司。

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