Publication:

探討活化的吞噬細胞對C2C12肌肉細胞移動速度的影響

骨骼肌具有自我再生的能力，透過位於肌纖維膜及基底層的肌肉前趨細胞進行增生及分化，最後形成具有功能性的肌纖維。當肌肉損傷時會產生一連串的免疫反應，嗜中性白血球、單核球及巨噬細胞會移至損傷部位，然後釋放相關的發炎物質，促進發炎反應進行，這些物質可以吸引肌肉前趨細胞移至損傷部位，使肌纖維得到修復。

研究指出，高濃度的腫瘤壞死因子-α (TNF-α)及介白素-6 (IL-6)會造成骨骼肌蛋白質流失及肌肉萎縮，因此，本研究擬觀察活化的吞噬細胞所分泌的TNF-α及IL-6對C2C12肌肉細胞移動能力的影響。結果發現，巨噬細胞釋放的TNF-α及IL-6會造成肌原母細胞及肌小管細胞的移動速度變慢。此外，單純外加細胞激素TNF-或IL-6同樣也會抑制肌原母細胞及肌小管細胞的移動速度，因此我們認為，TNF-α及IL-6可能與肌肉細胞的移動速度相關。

此外，運動時肌肉組織往往是處於較低氧氣濃度的狀態下，因此我們也觀察在低氧條件下活化的吞噬細胞培養液對肌肉細胞移動能力的影響。結果發現，低氧會減慢肌原母細胞及肌小管細胞的移動速度，而加入活化後的吞噬細胞培養液對肌原母細胞及肌小管細胞的移動抑制更為明顯。我們認為在低氧環境中，肌肉細胞的正常功能及代謝可能會跟著改變，進而影響其移動速度。另外，實驗結果也發現，無論在正常氧分壓或低氧環境下，肌小管細胞的移動速度都比肌原母細胞慢，其原因可能是因為在正常的生理過程中，肌纖維的再生能力主要是透過肌原母細胞的增生及分化來完成。

Skeletal muscle has the ability to regenerate fully functional myofibers by the proliferation and differentiation of myogenic precursor cells that are located in the sarcolemma and basal layers. Muscle injury triggers a series of immune responses. Neutrophils, monocytes and macrophages migrate to the injury site and release proinflammatory factors that promote acute inflammation and attract myegenic precursors migrate to the injury site and repair injured myofibers.

Studies indicate that high concentrations of TNF-α and IL-6 lead to a significant loss of skeletal muscle protein and muscular dystrophy. Therefore, the aim of this study was to investigate the effects of TNF-α and IL-6 secreted by activated macrophages on the migration of C2C12-derived myogenic cells. Results show that TNF-α and IL-6 secreted by activated macrophages suppressed the myoblasts and myotubes migration. Therefore, we regard that TNF-α and IL-6 may be related to the migration speed of myogenic cells.

Besides, muscle tissue is frequently exposed to hypoxia during exercise. Therefore, we also observed the effects of activated macrophage conditioned medium to the migration of myogenic cells under hypoxia. Results show that the myoblasts and myotubes migration was inhibited by hypoxia. In addition, activated macrophage conditioned medium further suppressed the myoblasts and myotubes migration. On the other hand, experimental results reveal that myotubes migrate slower than myobalsts under normoxia and hypoxia. This may be due to the fact that myofibers regeneration depends on myoblasts proliferation and differentiation in normal physiological processes.