失神经支配后经皮电刺激通过Wnt通路促进卫星细胞分化的机制研究

Wnt signaling pathway plays a most important role in satellite cell differentiation. In our previous research, we have found enhanced satellite cell differentiation by electrical stimulation after muscle denervation, which is positively correlated with improved muscle structure and function, but the molecular mechanisms of this effect and the role of Wnt signaling pathway still remain unknown. In the present study, we will observe the possible changes of Wnt proteins induced by electrical stimulation after sciatic nerve crush on rats; and then we'll isolate single myofibers from denervated muscles and perform electrical stimulation in vitro. In this way, we’ll further investigate whether changes in Wnt paracrine function of myofibers and activity of GSK3β, a modulator of Wnt, are responsible for the improvement of satellite cell differentiation by eletrical stimulation after denervation. Our aim is to find out the possible effects of Wnt signaling pathway on improved satellite cell differentiation, and to reveal the molecular mechanisms of enhanced satellite cell differentiation by electrical stimulation after denervation. This will provide important evidences to support the clinical application of electrical stimulation in patients with nerve injury as well as other musculoskeletal diseases attributed to impaired satellite cell differentiation. It is hopeful that electrical stimulation will be widely used to promote patients’ function recovery and improve the quality of their daily lives.

Wnt通路是骨骼肌卫星细胞分化的关键通路。我们的前期研究表明，经皮电刺激治疗能明显促进失神经支配后卫星细胞的分化，且这一促进作用与骨骼肌结构和收缩功能的改善呈正相关，但其分子机制及Wnt通路在这一过程中的作用尚不明确。本研究拟建立大鼠坐骨神经不全损伤模型，给予经皮电刺激治疗后观察失神经支配骨骼肌内Wnt通路重要蛋白的表达变化；再从失神经支配骨骼肌中分离单根肌纤维进行体外培养和电刺激，进一步探索Wnt通路重要调节因子GSK3β活性及肌纤维Wnt蛋白旁分泌活动的变化与电刺激促进卫星细胞分化的关系，从而明确Wnt通路在卫星细胞分化增强的过程中起到的作用，在分子水平上进一步阐述电刺激促进失神经支配后卫星细胞分化的可能机制，为经皮电刺激治疗骨骼肌失神经支配的临床应用提供依据，并有助于将这一治疗措施推广至其他因卫星细胞分化不良导致的疾病，使受累肌肉功能得到最大程度的恢复，具有较广阔的应用前景。