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硫化氢作为治疗杜氏肌营养不良症和其他肌肉相关疾病的治疗选择。

Hydrogen sulfide as a therapeutic option for the treatment of Duchenne muscular dystrophy and other muscle-related diseases.

机构信息

Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387, Kraków, Poland.

出版信息

Cell Mol Life Sci. 2022 Nov 28;79(12):608. doi: 10.1007/s00018-022-04636-0.

Abstract

Hydrogen sulfide (HS) has been known for years as a poisoning gas and until recently evoked mostly negative associations. However, the discovery of its gasotransmitter functions suggested its contribution to various physiological and pathological processes. Although HS has been found to exert cytoprotective effects through modulation of antioxidant, anti-inflammatory, anti-apoptotic, and pro-angiogenic responses in a variety of conditions, its role in the pathophysiology of skeletal muscles has not been broadly elucidated so far. The classical example of muscle-related disorders is Duchenne muscular dystrophy (DMD), the most common and severe type of muscular dystrophy. Mutations in the DMD gene that encodes dystrophin, a cytoskeletal protein that protects muscle fibers from contraction-induced damage, lead to prominent dysfunctions in the structure and functions of the skeletal muscle. However, the main cause of death is associated with cardiorespiratory failure, and DMD remains an incurable disease. Taking into account a wide range of physiological functions of HS and recent literature data on its possible protective role in DMD, we focused on the description of the 'old' and 'new' functions of HS, especially in muscle pathophysiology. Although the number of studies showing its essential regulatory action in dystrophic muscles is still limited, we propose that HS-based therapy has the potential to attenuate the progression of DMD and other muscle-related disorders.

摘要

硫化氢(HS)多年来一直被认为是一种有毒气体,直到最近才引起了人们的关注。然而,其气体递质功能的发现表明它参与了各种生理和病理过程。尽管 HS 已被发现通过调节抗氧化、抗炎、抗凋亡和促血管生成反应来发挥细胞保护作用,但迄今为止,其在骨骼肌肉病理生理学中的作用尚未得到广泛阐明。与肌肉相关的疾病的典型例子是杜氏肌营养不良症(DMD),这是最常见和最严重的肌肉营养不良症。编码肌营养不良蛋白的 DMD 基因突变,肌营养不良蛋白是一种保护肌肉纤维免受收缩引起的损伤的细胞骨架蛋白,导致骨骼肌结构和功能的明显异常。然而,主要的死亡原因与心肺功能衰竭有关,DMD 仍然是一种无法治愈的疾病。考虑到 HS 的广泛生理功能以及最近关于其在 DMD 中可能具有保护作用的文献数据,我们专注于描述 HS 的“旧”和“新”功能,特别是在肌肉病理生理学方面。尽管表明其在萎缩肌肉中具有重要调节作用的研究数量仍然有限,但我们提出基于 HS 的治疗方法有可能减轻 DMD 及其他与肌肉相关的疾病的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21e8/9705465/00cbb9aeb727/18_2022_4636_Fig1_HTML.jpg

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