骨骼肌损伤修复过程中肌再生调控因子和趋化因子的作用研究

The mechanism of skeletal muscle regeneration is becoming a hot topic worldwide. Muscle satellite cells are the focus of these studies. Macrophages are indispensable because they are involved in the regulation of skeletal muscle regeneration, angiogenesis and fibrosis. However, these studies focus on the muscle injury induced by toxins injection or muscular dystrophy, paying less attention to the skeletal muscle contusion, which is the most common injury in the field of sports medicine. The mechanisms of skeletal muscle regeneration are still not clear, especially the two key steps of regeneration, for instance, what factors released from injured muscle are involved in promoting the migration of monocytes/macrophages and muscle satellite cells, what factors are involved in muscle satellite cell activation, proliferation, and differentiation. In addition, the clinical treatment of severe skeletal injury is also limited and inadequately developed by the absence of effective local pharmacologic intervention. In this research, we will establish an animal model of skeletal muscle injury, combined with an in vivo model of macrophage elimination, to investigate the factors involved in the migration of monocytes/macrophages and muscle satellite cells, and the factors involved in muscle satellite cells activation, proliferation, and differentiation. Moreover, exogenous key factors are administrated locally to explore their effects and possible mechanisms in the intervention of the repair process. Our research project is expected to develop the potential pharmacologic treatment of severe skeletal muscle injury for clinical research and practice.

骨骼肌损伤修复机理的研究正成为国内外研究的热点，肌卫星细胞是研究的焦点。此外，巨噬细胞的作用不可或缺，它参与调控骨骼肌再生、血管再生和纤维化形成。这些研究多采用注射毒素致伤、肌营养不良症等模型，而较少涉及骨骼肌挫伤这类运动医学领域最常见的损伤。对挫伤修复机制的研究还很不够，特别是肌肉挫伤后释放了哪些信号募集外周血单核/巨噬细胞、促进肌卫星细胞迁移从而启动修复，哪些因子参与肌卫星细胞激活、增殖、分化这两大骨骼肌再生的核心问题仍有待阐明。此外，外源性药物局部干预治疗骨骼肌损伤、促进修复的手段较少。因此，本研究通过建立骨骼肌挫伤模型和巨噬细胞剔除模型，围绕骨骼肌再生的两大核心问题展开，试图探明影响肌卫星细胞和巨噬细胞迁移的首要因素、影响肌卫星细胞激活、增殖、分化的关键因子；并在体观察这些关键因子局部干预对骨骼肌修复效果的影响，对相关机制展开探索，为临床应用这些因子治疗骨骼肌损伤提供实验依据。

骨骼肌损伤修复机理的研究正成为国内外研究的热点，肌卫星细胞是研究的焦点。此外，巨噬细胞的作用不可或缺，它参与调控骨骼肌再生、血管再生和纤维化形成。这些研究多采用注射毒素致伤、肌营养不良症等模型，而较少涉及骨骼肌挫伤这类运动医学领域最常见的损伤。对挫伤修复机制的研究还很不够，特别是肌肉挫伤后释放了哪些信号募集外周血单核/巨噬细胞、促进肌卫星细胞迁移从而启动修复，哪些因子参与肌卫星细胞激活、增殖、分化这两大骨骼肌再生的核心问题仍有待阐明。此外，外源性药物局部干预治疗骨骼肌损伤、促进修复的手段较少。因此，本研究通过建立骨骼肌挫伤模型和巨噬细胞剔除模型，围绕骨骼肌再生的两大核心问题展开，试图探明影响肌卫星细胞和巨噬细胞迁移的首要因素、影响肌卫星细胞激活、增殖、分化的关键因子；并在体观察这些关键因子局部干预对骨骼肌修复效果的影响，对相关机制展开探索。结果表明，骨骼肌损伤后多种肌再生因子和趋化因子表达上调，且具有严格的时序性，它们可能参与了损伤骨骼肌再生。对巨噬细胞与骨骼肌再生关系的研究表明，剔除巨噬细胞可通过加剧再生后期阶段炎症和氧化应激水平损害骨骼肌再生。此外，巨噬细胞源性肌再生调节因子在骨骼肌再生中具有重要作用。通过骨骼肌损伤后因子变化规律，及巨噬细胞剔除后相关因子的改变，及相关离体实验结果，初步探明了影响骨骼肌再生的关键因子。我们用这些关键再生调节因子局部干预损伤骨骼肌，发现它们有助于损伤骨骼肌形态学改善。这些研究将为临床应用这些因子治疗骨骼肌损伤提供实验依据。