Nuutila Kristo, Sakthivel Dharaniya, Kruse Carla, Tran Peter, Giatsidis Giorgio, Sinha Indranil
Division of Plastic Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Wound Repair Regen. 2017 May;25(3):408-413. doi: 10.1111/wrr.12547. Epub 2017 May 26.
Volumetric muscle loss (VML), usually occurring following traumatic injury, results in a composite loss of muscle mass. These injuries manifest as decreased strength and functional impairments. Clinically, these injuries often heal with fibrosis, as opposed to skeletal muscle regeneration. This study examines the healing patterns of a skeletal muscle following VML in a murine model. Eight-week old male C57BL/6J mice used in the study underwent either bilateral VML injury or cryoinjury, a widely used model known to induce skeletal muscle regeneration. Skeletal muscle was harvested at 2 and 4 weeks following injury and subjected to histological analysis. H&E staining demonstrated skeletal muscle regeneration following cryoinjury, but not VML, at either timepoint post-injury. Additionally, samples were analyzed using a wound-healing PCR array to identify differentially regulated genes of interest in VML and cryoinjury, as compared to noninjured controls. The gene array data further demonstrated prolonged inflammation and increased pro-fibrotic activity in the VML injured muscles, as compared to cryoinjury. In addition, IGF1, a known myogenic factor, was significantly decreased following VML, as compared to cryoinjury, in both ELISA and PCR. This study offers an insight into the pathophysiology of VML injury and reveals a gene profile of a nonregenerating skeletal muscle.
容积性肌肉损失（VML）通常发生在创伤性损伤之后，会导致肌肉质量的综合损失。这些损伤表现为力量下降和功能障碍。临床上，这些损伤常以纤维化方式愈合，而非骨骼肌再生。本研究在小鼠模型中研究了VML后骨骼肌的愈合模式。研究中使用的8周龄雄性C57BL/6J小鼠接受了双侧VML损伤或冷冻损伤，冷冻损伤是一种广泛使用的可诱导骨骼肌再生的模型。在损伤后2周和4周采集骨骼肌并进行组织学分析。苏木精-伊红（H&E）染色显示，在损伤后的任何时间点，冷冻损伤后骨骼肌发生了再生，但VML后未发生再生。此外，与未受伤的对照组相比，使用伤口愈合PCR阵列分析样本，以鉴定VML和冷冻损伤中差异调节的感兴趣基因。基因阵列数据进一步表明，与冷冻损伤相比，VML损伤的肌肉中炎症持续时间延长且促纤维化活性增加。此外，在酶联免疫吸附测定（ELISA）和聚合酶链反应（PCR）中，与冷冻损伤相比，VML后已知的生肌因子胰岛素样生长因子1（IGF1）显著降低。本研究深入了解了VML损伤的病理生理学，并揭示了非再生骨骼肌的基因谱。
