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一氧化氮在肌肉生成和治疗性肌肉修复中的作用。

Nitric oxide in myogenesis and therapeutic muscle repair.

机构信息

Unit of Clinical Pharmacology, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences L. Sacco, University Hospital Luigi Sacco, Università di Milano, Via GB Grassi 74, 20157 Milan, Italy.

出版信息

Mol Neurobiol. 2012 Dec;46(3):682-92. doi: 10.1007/s12035-012-8311-8. Epub 2012 Jul 22.

Abstract

Nitric oxide is a short-lived intracellular and intercellular messenger. The first realisation that nitric oxide is important in physiology occurred in 1987 when its identity with the endothelium-derived relaxing factor was discovered. Subsequent studies have shown that nitric oxide possesses a number of physiological functions that are essential not only to vascular homeostasis but also to neurotransmission, such as in the processes of learning and memory and endocrine gland regulation, as well as inflammation and immune responses. The discovery in 1995 that a splice variant of the neuronal nitric oxide synthase is localised at the sarcolemma via the dystrophin-glycoprotein complex and of its displacement in Duchenne muscular dystrophy has stimulated a host of studies exploring the role of nitric oxide in skeletal muscle physiology. Recently, nitric oxide has emerged as a relevant messenger also of myogenesis that it regulates at several key steps, especially when the process is stimulated for muscle repair following acute and chronic muscle injuries. Here, we will review briefly the mechanisms and functions of nitric oxide in skeletal muscle and discuss its role in myogenesis, with specific attention to the promising nitric oxide-based approaches now being explored at the pre-clinical and clinical level for the therapy of muscular dystrophy.

摘要

一氧化氮是一种短寿命的细胞内和细胞间信使。1987 年,当发现其与内皮衍生的松弛因子具有相同的身份时,人们第一次认识到一氧化氮在生理学中的重要性。随后的研究表明,一氧化氮具有多种生理功能,不仅对血管稳态至关重要,而且对神经递质也至关重要,如在学习和记忆过程以及内分泌腺调节中,以及炎症和免疫反应中。1995 年发现,神经元型一氧化氮合酶的剪接变体通过肌营养不良蛋白聚糖复合物定位于肌膜,并在杜氏肌营养不良症中发生位移,这激发了大量研究探索一氧化氮在骨骼肌生理学中的作用。最近,一氧化氮作为一种相关的信使也出现在肌发生中,它在几个关键步骤中调节肌发生,特别是在急性和慢性肌肉损伤后为肌肉修复而刺激肌发生时。在这里,我们将简要回顾一氧化氮在骨骼肌中的作用机制和功能,并讨论其在肌发生中的作用,特别关注目前在临床前和临床水平上探索的基于一氧化氮的有前途的方法,用于治疗肌肉营养不良症。

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