关于肌卫星细胞移植模式对于老年肌肉衰减综合征治疗效果的基础研究

Increasingly, the worldwide population is growing older. Sarcopenia occurs with age and is characterized by loss of muscle bulk and performance. Mechanisms that underlie this process are beginning to be understood. The regeneration of skeletal muscle is largely dependent on a small population of resident cells termed satellite cells. However, evidence implies that satellite cells could play some limiting role in aged muscle undergoing repair or maintenance of mass, and observed a decrease in satellite cell number, which is of potential clinical concern as this could contribute to sarcopenia. Thus, it is hypothesized that satellite cell supplement (transplantation) can prevent and treat sarcopenia. As an important part of the research, must want to clear the best transplant conditions (delivery route and dosage), evaluate to determine the effects of the skeletal muscle satellite cells transplantation on muscle bulk and performance. Therefore, in our study, we will be test the hypothesis that skeletal muscle satellite cell transplantation can prevent and treat sarcopenia (decline in muscle bulk and performance) in the old mice, and determine the best conditions of transplantation. In addition, we also will be examine the effects of combinations of skeletal muscle satellite cells transplantation and exercise training on sarcopenia in the old mice. Further clearing of methods and effects of skeletal muscle satellite cells transplantation on sarcopenia will be important for discovering novel treatment strategies.

随着社会老龄化的进展，以增龄性骨骼肌质量和功能下降为特征的老年肌肉衰减综合征对老年人群及整个社会发展的危害性日益严峻。近来，肌卫星细胞作为一种在肌肉组织中少量存在的肌肉干细胞，它对老年肌肉衰减综合征的发生机制的影响备受关注。骨骼肌细胞的肥大、修复和再生主要是通过肌卫星细胞的分化增殖来实现的，但是衰老可以引起卫星细胞数量的减少及分化增殖能力的明显减弱。有研究证实，肌卫星细胞数量的减少是老年肌肉衰减综合征的重要发生机制之一。因此，我们假设肌卫星细胞的补充（移植）可以防治老年肌肉衰减综合征。作为验证此假说的关键性基础研究，在本研究中，我们将利用动物实验探讨对于防治老年肌肉衰减综合征肌，卫星细胞的最佳移植模式（途径和用量）和对骨骼肌质量和功能的影响，以及其与运动疗法联合治疗效果的有无，以期待为开发新的老年肌肉衰减综合征的防治方法提供可靠的理论依据。

肌卫星细胞是肌肉组织中少量存在的干细胞。目前,因其对老年肌肉衰减综合征(sarcopenia)发生机制的影响而备受关注。骨骼肌细胞的肥大、修复和再生主要是通过肌卫星细胞的增殖分化来实现的，但是衰老可以引起卫星细胞数量的减少及增殖分化能力的明显减弱。有研究证实，肌卫星细胞数量的减少是sarcopenia的重要发生机制之一。因此，我们假设肌卫星细胞的移植可以防治sarcopenia。在本研究中我们通过对高龄小鼠进行肌卫星细胞移植和运动疗法，研究了肌卫星细胞的最佳移植条件（途径和用量），和对骨骼肌质量和功能的影响，以及它们的联合治疗效果。.本研究结果显示肌卫星细胞移植可以有效改善小鼠的sarcopenia症状。肌肉局部植入对于sarcopenia模型小鼠的骨骼肌质量以及功能的改善效果明显优于静脉植入。此外，肌肉注射中等浓度（5000个/100ul）干细胞溶液是治疗小鼠sarcopenia的相对高效率的剂量，但是，植入低浓度（500个/100ul）干细胞溶液对小鼠sarcopenia的改善效果明显低于中等强度，植入高浓度（10000个/100ul）干细胞溶液的改善效果与中等浓度剂量无统计学差异。通过骨骼肌局部注射肌卫星细胞移植和运动疗法的长期观察，我们发现两种干预均可改善sarcopenia小鼠的肌肉质量和功能，且两者联合治疗效果优于各自单独的效果。.我们的研究结果提示肌肉注射中等浓度的干细胞溶液是治疗小鼠sarcopenia的相对高效手段；并且联合运动疗法对于治疗小鼠sarcopenia症状可产生更好的改善效果。本研究为开发新的sarcopenia的防治方法提供了可靠的理论依据。