Molecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, California, USA.
Compr Physiol. 2011 Oct;1(4):2029-62. doi: 10.1002/cphy.c100092.
Skeletal muscle continuously adapts to changes in its mechanical environment through modifications in gene expression and protein stability that affect its physiological function and mass. However, mechanical stresses commonly exceed the parameters that induce adaptations, producing instead acute injury. Furthermore, the relatively superficial location of many muscles in the body leaves them further vulnerable to acute injuries by exposure to extreme temperatures, contusions, lacerations or toxins. In this article, the molecular, cellular, and mechanical factors that underlie muscle injury and the capacity of muscle to repair and regenerate are presented. Evidence shows that muscle injuries that are caused by eccentric contractions result from direct mechanical damage to myofibrils. However, muscle pathology following other acute injuries is largely attributable to damage to the muscle cell membrane. Many feaures in the injury-repair-regeneration cascade relate to the unregulated influx of calcium through membrane lesions, including: (i) activation of proteases and hydrolases that contribute muscle damage, (ii) activation of enzymes that drive the production of mitogens and motogens for muscle and immune cells involved in injury and repair, and (iii) enabling protein-protein interactions that promote membrane repair. Evidence is also presented to show that the myogenic program that is activated by acute muscle injury and the inflammatory process that follows are highly coordinated, with myeloid cells playing a central role in modulating repair and regeneration. The early-invading, proinflammatory M1 macrophages remove debris caused by injury and express Th1 cytokines that play key roles in regulating the proliferation, migration, and differentiation of satellite cells. The subsequent invasion by anti-inflammatory, M2 macrophages promotes tissue repair and attenuates inflammation. Although this system provides an effective mechanism for muscle repair and regeneration following acute injury, it is dysregulated in chronic injuries. In this article, the process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury, to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle.
骨骼肌通过基因表达和蛋白质稳定性的改变来不断适应其力学环境的变化，从而影响其生理功能和质量。然而，机械应力通常超过诱导适应性的参数，导致急性损伤。此外，由于身体许多肌肉的位置相对较浅，它们更容易受到极端温度、挫伤、撕裂或毒素的急性损伤。在本文中，介绍了肌肉损伤的分子、细胞和力学因素以及肌肉修复和再生的能力。有证据表明，由离心收缩引起的肌肉损伤是由于肌原纤维的直接机械损伤。然而，其他急性损伤后的肌肉病理学主要归因于肌肉细胞膜的损伤。损伤修复再生级联中的许多特征与膜损伤导致的钙不受调节内流有关，包括：（i）激活蛋白酶和水解酶，导致肌肉损伤；（ii）激活驱动与损伤和修复相关的肌肉和免疫细胞中的有丝分裂原和运动原产生的酶；（iii）促进促进膜修复的蛋白质-蛋白质相互作用。有证据表明，急性肌肉损伤激活的成肌程序和随后的炎症过程高度协调，髓细胞在调节修复和再生中起着核心作用。早期浸润的、促炎的 M1 巨噬细胞清除损伤引起的碎片，并表达 Th1 细胞因子，在调节卫星细胞的增殖、迁移和分化中发挥关键作用。随后浸润的抗炎性 M2 巨噬细胞促进组织修复并减弱炎症。虽然该系统为急性损伤后肌肉修复和再生提供了有效的机制，但它在慢性损伤中失调。在本文中，以肌肉营养不良中的肌肉损伤为例，突出了急性和慢性损伤肌肉中损伤和修复过程的相似性和差异性，说明了肌肉损伤、修复和再生的过程。
