蓓萨罗丁调控MyoD促进肌卫星细胞增殖分化在脊髓损伤后骨骼肌萎缩中的作用及机制研究

脊髓损伤后骨骼肌萎缩严重影响患者的生活质量，迄今为止尚无有效治疗手段。目前发现维甲酸X受体（RXR）的激动剂蓓萨罗丁（Bex）能够促进肌损伤的恢复，但其促进肌卫星细胞（MSC）的增殖分化在脊髓损伤后骨骼肌萎缩中的作用及机制尚不清楚。研究证实成肌分化抗原（MyoD）可以促进MSC增殖分化减轻肌萎缩。我们预实验发现：Bex能够增加脊髓损伤后骨骼肌纤维的横截面积，并促进原代培养的MSC分泌胰岛素样生长因子-2（IGF-2）。因此，我们提出假说：Bex通过激活RXRα提高MSC分泌IGF-2，调控MyoD表达，促进MSC增殖分化治疗脊髓损伤后骨骼肌萎缩。为证实这一假说，我们将利用分子生物学、细胞学及病理学等技术方法，从分子、细胞及动物水平探讨Bex参与MSC增殖分化作用及修复脊髓损伤后骨骼肌萎缩的机制。本项目将为研究脊髓损伤后骨骼肌萎缩的发病机理提供新思路，并为其防治提供新药物。

Up to now, there is no effective treatment for skeletal muscle atrophy after spinal cord injury (SCI) that seriously affects the patient’s life quality. The retinoid X receptor agonist (Bexarotene) was currently found to promote the recovery of muscle injury. However, it is still unclear that the effects and mechanisms of regulating the proliferation and differentiation of muscle satellite cells (MSC) by Bex in the skeletal muscle atrophy after SCI. Moreover, myogenic differentiation antigen (MyoD) was confirmed to promote the proliferation and differentiation of MSC to alleviate muscular atrophy. In our preliminary experiment, we found that Bex could increase the cross-sectional area of skeletal muscle fibers after SCI, and promote the primary MSC to secrete insulin-like growth factor-2 (IGF-2). Therefore, we propose the hypothesis that The RXRα is actived by Bex to enhance the secretion of IGF-2, and regulate the expression of MyoD for promoting the proliferation and differentiation of MSC to treat skeletal muscle atrophy after SCI. To confirm this hypothesis, we will research on the effects of promoting the proliferation and differentiation of MSC by Bex, and the mechnisms of repairing skeletal muscle atrophy after SCI with molecular biology, cytology, pathology and other technical methods at the molecular, cellular and animal levels.In this project, we will offer an innotive idea for studying the pathogenesis and provide a new drug for skeletal muscle atrophy after SCI.