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双醋瑞因改善mdx小鼠膈肌的营养不良表型

Dystrophic phenotype improvement in the diaphragm muscle of mdx mice by diacerhein.

作者信息

Mâncio Rafael Dias, Hermes Túlio de Almeida, Macedo Aline Barbosa, Mizobuti Daniela Sayuri, Rupcic Ian Feller, Minatel Elaine

机构信息

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

出版信息

PLoS One. 2017 Aug 7;12(8):e0182449. doi: 10.1371/journal.pone.0182449. eCollection 2017.

Abstract

Chronic inflammation and oxidative stress are striking features of Duchenne muscular dystrophy disease. Diacerhein is an anthraquinone, which exhibits anti-inflammatory and antioxidant properties. Based on their actions, the present study evaluated the effects of diacerhein against myonecrosis, oxidative stress and inflammatory response in the diaphragm muscle of mdx mice and compared these results to current treatment widely used in DMD patients, with a main focus on the impact of prednisone. The results demonstrated that diacerhein treatment prevented muscle damage indicated by a decrease in the IgG uptake by muscle fibers, lower CK levels in serum, reduction of fibers with central nuclei with a concomitant increase in fibers with peripheral nuclei. It also had an effect on the inflammatory process, decreasing the inflammatory area, macrophage staining and TNF-α and IL-1β content. Regarding oxidative stress, diacerhein treatment was effective in reducing the ROS and lipid peroxidation in the diaphragm muscle from mdx mice. Compared to prednisone treatment, our findings demonstrated that diacerhein treatment improved the dystrophic phenotype in the diaphragm muscle of mdx mice similar to that of glucocorticoid therapy. In this respect, this work suggests that diacerhein has a potential use as an alternative drug in dystrophinopathy treatment and recommends that its anti-inflammatory and antioxidants properties in the dystrophic muscle should be better understood.

摘要

慢性炎症和氧化应激是杜兴氏肌营养不良症的显著特征。双醋瑞因是一种蒽醌,具有抗炎和抗氧化特性。基于其作用,本研究评估了双醋瑞因对mdx小鼠膈肌肌坏死、氧化应激和炎症反应的影响,并将这些结果与目前在杜氏肌营养不良症患者中广泛使用的治疗方法进行比较,主要关注泼尼松的影响。结果表明,双醋瑞因治疗可预防肌肉损伤,表现为肌纤维对IgG摄取减少、血清中肌酸激酶水平降低、中央核纤维减少,同时外周核纤维增加。它还对炎症过程有影响,减少炎症面积、巨噬细胞染色以及肿瘤坏死因子-α和白细胞介素-1β含量。关于氧化应激,双醋瑞因治疗可有效降低mdx小鼠膈肌中的活性氧和脂质过氧化。与泼尼松治疗相比,我们的研究结果表明,双醋瑞因治疗改善了mdx小鼠膈肌的营养不良表型,类似于糖皮质激素治疗。在这方面,这项工作表明双醋瑞因有潜力作为治疗肌营养不良症的替代药物,并建议应更好地了解其在营养不良肌肉中的抗炎和抗氧化特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71a6/5546703/e040d13780f3/pone.0182449.g001.jpg

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