BackgroundOrbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions.MethodsIn this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries.ResultsEvaluation of lip muscle regeneration till 56 days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (n = 6, fibrotic area 48.9% in the stretch group, P < 0.001, and 25.1% in the dissection group, P < 0.001). There was the lowest number of Pax7‐positive nuclei at Days 3 and 7 in the stretch group (n = 6, P < 0.001, P < 0.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra+ fibro‐adipogenic progenitors infiltrated area at Days 3, 7 and 14 (n = 6, P = 0.003, P = 0.006, P = 0.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (ε = 2688 μ strain) of mechanical strain (n = 3, P = 0.014, P = 0.023). RNA‐seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin‐10 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin‐10 in cultured satellite cells (n = 3, P = 0.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair.ConclusionsTensile force proved to be the most detrimental manoeuvre for post‐operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin‐10‐mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.

中文翻译：

---

张力损害白细胞介素-10调节下的唇部肌肉再生


背景口轮匝肌是说话、面部表情和美观的关键肌肉，被认为是最佳唇部修复的驱动力。肌肉再生受损仍然是手术结果不理想的主要原因。然而，缺乏关于不同手术操作如何影响唇部肌肉再生的研究，限制了寻求有效干预措施的努力。方法在本研究中，我们建立了大鼠唇部手术模型，其中口轮匝肌因解剖、横断和切割等操作而损伤。拉紧。通过肌生成和纤维生成的组织学分析来检查每种技术对肌肉再生的影响。通过体外对培养的成肌细胞施加机械应变，进一步研究了拉力的影响。对不同手术组的肌肉卫星细胞进行转录组分析，找出介导肌肉纤维化的关键因素，然后进行治疗干预以改善唇部手术后的肌肉再生。结果直到受伤后 56 天的唇部肌肉再生评估显示，拉伸组的结果是在最严重的肌肉纤维化中（n = 6，拉伸组纤维化面积为 48.9%，P < 0.001，解剖组为 25.1%，P < 0.001）。拉伸组中第 3 天和第 7 天的 Pax7 阳性细胞核数量最低（n = 6，P < 0.001，P < 0.001），表明卫星细胞扩增受损。横断组和拉伸组的肌生成均受损，中央有核肌纤维和胚胎 MyHC 峰值延迟证明了这一点。同时，拉伸组在第 3、7 和 14 天时 Pdgfra+ 纤维脂肪祖细胞浸润区域的百分比最高（n = 6，P = 0。003，P = 0.006，P = 0.037）。当培养的大鼠唇肌成肌细胞暴露于高强度（ε = 2688 μ应变）机械应变时，肌管形成和融合能力受损（n = 3，P = 0.014，P = 0.023）。对从不同手术组分离的卫星细胞进行的 RNA-seq 分析表明，白介素-10 是肌肉纤维化的关键调节因子。重组人Wnt7a可抑制培养卫星细胞中白介素-10的表达（n = 3，P = 0.041），对唇部修复手术拉伸损伤后口轮匝肌纤维化有改善作用。尽管它在矫正唇部和鼻子畸形方面发挥着关键作用，但它仍然是对术后唇部肌肉再生最有害的操作。调节白细胞介素 10 介导的炎症过程的辅助生物疗法可以在高手术张力条件下促进唇部肌肉再生。