外泌体的生物学作用与失神经肌萎缩

Biological role of exosomes in denervated muscle atrophy

背景:外周神经损伤在临床十分常见,但其再生速度很慢,通常在神经恢复过程中肌肉就已经发生不可逆萎缩,从而严重影响患者的生活质量,因此寻找一种有效的治疗失神经肌萎缩的方法显得尤为重要。目的:总结外泌体的生物学特性及其参与骨骼肌生成与萎缩的作用机制,重点综述失神经肌萎缩的过程以及外泌体在治疗失神经肌萎缩中的作用,以期为治疗失神经肌萎缩寻找到一条新途径。方法:检索PubMed数据库中的相关文章,英文检索词为“exosome,skeletal muscle,muscle atrophy,muscle regenerate,peripheral nerve injury,denervation muscle atrophy”;检索知网、万方数据库,中文检索词为“外泌体,骨骼肌,周围神经损伤,肌萎缩,肌肉再生,神经修复,失神经肌萎缩”,并结合文献追溯法查找部分文献。结果与结论:①外泌体广泛分布于各种体液中,通过旁分泌或自分泌作用于受体细胞,影响受体细胞表型;②外泌体在肌肉中的主要功能可能与RNA的递送有关,肌细胞分泌或摄取的外泌体miRNA参与肌肉的发育、生长、适应和再生;③周围神经损伤后肌肉失去神经的运动控制作用和营养支持作用,而后凋亡和蛋白水解增加,导致肌肉萎缩;④不同细胞来源外泌体通过直接或间接的方式修复损伤神经,进而缓解肌肉萎缩,经初步证实外泌体可能同样以miRNA依赖的方式介导相关再生基因的表达调控以促进神经再生,因此外泌体可作用于神经细胞延缓失神经肌萎缩。

BACKGROUND:Peripheral nerve injury is very common in clinic,but its regeneration rate is very slow.During nerve recovery,muscle atrophy has already occurred irreversibly,which seriously affects the quality of life of patients.Therefore,it is particularly important to find an effective method for the treatment of denervated muscle atrophy.OBJECTIVE:To summarize the biological characteristics of exosomes and their mechanisms of involvement in skeletal muscle formation and atrophy,focus on the process of denervated muscle atrophy and the role of exosomes in the treatment of denervated muscle atrophy,providing a new method for the treatment of denervated muscle atrophy.METHODS:Relevant articles were searched on PubMed database with English search words“exosome,skeletal muscle,muscle atrophy,muscle regenerate,peripheral nerve injury,denervation muscle atrophy”.Related articles were searched on Wanfang and CNKI databases,and the Chinese search words were“exosome,skeletal muscle,peripheral nerve injury,muscle atrophy,muscle regeneration,nerve repair,denervated muscle atrophy”,and some articles were searched with literature retrospective method.RESULTS AND CONCLUSION:(1)Exosomes are widely distributed in all kinds of body fluids.They act on recipient cells through paracrine or autocrine and affect the phenotype of recipient cells.(2)The main function of exosomes in muscle may be related to the delivery of RNA.Exosomal miRNAs secreted or ingested by muscle cells are involved in muscle development,growth,adaptation and regeneration.(3)After peripheral nerve injury,muscle loses its motor control and nutritional support,and then apoptosis and proteolysis increase,leading to muscle atrophy.(4)Exosomes from different cell sources repair injured nerves directly or indirectly,thereby alleviating muscle atrophy.It has been preliminarily confirmed that exosomes may also mediate the expression regulation of related regenerative genes in a miRNA-dependent manner to promote neural regeneration.Therefore,exosomes can act on nerve cells and delay denervated muscle atrophy.