运动协同经血干细胞通过BDNF-PI3K/Akt-CREB通路促进脊髓损伤轴突再生的机制研究

脊髓损伤（SCI）是一种严重的致残性疾病，目前尚缺乏有效的治疗手段。近年来，运动训练联合干细胞修复SCI的治疗方案已受到研究者的广泛关注。我们前期的研究发现，运动联合经血干细胞（MenSCs）移植可更好的促进SCI大鼠后肢运动功能恢复，并可增加损伤脊髓BDNF和CREB的表达，促进轴突再生。BDNF可通过PI3K/Akt发挥神经保护作用，但运动联合MenSCs是否通过该机制促进轴突再生，目前尚不明确。因此，我们提出假说：运动训练联合MenSCs可发挥协同作用，并通过激活BDNF-PI3K/Akt-CREB通路，促进轴突再生，改善SCI后的肢体功能恢复。为验证该假说，我们将在细胞、信号通路和基因调控等层面探讨两者联合促进SCI后轴突再生和改善SCI大鼠肢体运动功能的具体机制。本课题将有助于明确两者发挥协同作用的作用机制，为SCI后的再生康复提供理论依据，为SCI的康复治疗提供一种新的思路。

Spinal cord injury (SCI) is a serious disabling disease, and there is still lack of effective treatment. recently, the therapy of exercise training combined with stem cell repair of SCI has received extensive attention from researchers. Our previous study found that exercise combined with Menstrual blood-derived mesenchymal stem cells (MenSCs) transplantation could better promote the recovery of hindlimb motor function of SCI rats, and increase the expression of BDNF and CREB in injured spinal cord and enhance axon regeneration. BDNF can exert neuroprotective effects through PI3K/Akt, but whether exercise combined with MenSCs can exert axon regeneration through this mechanism remains unclear. Therefore, we propose the hypothesis that exercise training combined with MenSCs can play a synergistic role and enhance axon regeneration and improve limb function recovery after SCI by activating the BDNF-PI3K/Akt-CREB pathway. To test this hypothesis, we will explore the specific mechanism of the combination of the two intervention methods in promoting axon regeneration and improving limb motor function in SCI rats at the cellular, signaling and gene regulation levels. This study will help us to clarify the mechanism of synergy between exercise and MenSCs, provide theoretical basis for regenerative rehabilitation after SCI, and provide a new idea for rehabilitation treatment of SCI.