IGF-1/PI3K/Akt信号通路参与低频电刺激治疗废用性骨骼肌萎缩的机制研究

Skeletal muscle disuse atrophy (SMDA) is induced by decreased mechanical signal from many diseases, affecting mobility and daily activities of patients. Low frequency electrical stimulation (LFES) provides mechanical load and prevents SMDA through increasing fiber cross-sectional area and muscle tetanic force, but the mechanism is far from clear. Our study has shown that LFES promotes proliferation of skeletal muscle stem cells (satellite cells), indicating the important role of satellite cell proliferation in SMDA treatment, however, the mechanism of satellite cell proliferation is not clear. It has been demonstrated that LFES upregulates Insulin-like growth factor-1 (IGF-1) in skeletal muscle by increasing mechanical load, and exogenous IGF-1 promotes cell proliferation via PI3K/Akt signal pathway in vitro. Our study has established hindlimb suspension-induced SMDA model, the effects of LFES on IGF-1, PI3K, Akt expression and satellite cell proliferation, as well as effects of exogenous IGF-1 on isolated satellite cells will be stressed. The important role of IGF-1/PI3K/Akt signal pathway in promoting satellite cell proliferation induced by LFES will be explored at molecular, cellular and tissue level. Our study will provide new ideas for stem cell-based treatment for muscle atrophy.

废用性骨骼肌萎缩（SMDA）是由于多种疾病引起机械负荷减小导致骨骼肌形态和功能改变，严重影响患者的运动功能和日常生活。低频电刺激（LFES）可通过增大肌纤维的横截面积，增加肌肉的强直收缩力起到治疗SMDA的作用，但其机理仍不清楚。我们的前期研究表明，LFES可促进骨骼肌干细胞（卫星细胞）的增殖，提示LFES通过促进卫星细胞增殖治疗SMDA的重要作用。LFES可上调胰岛素样生长因子-1（IGF-1）的表达，并且离体实验已证明外源性IGF-1可通过激活PI3K/Akt信号传导通路刺激细胞的增殖。本课题已建立尾悬吊小鼠SMDA模型，研究LFES 对骨骼肌IGF-1及PI3K、Akt表达及卫星细胞增殖的影响，结合IGF-1对分离纯化的卫星细胞的影响，从分子、细胞、组织水平探讨IGF-1/PI3K/Akt信号传导通路可能介导LFES促进卫星细胞增殖的关键作用，为临床基于干细胞治疗肌肉萎缩提供新思路。