Rabinovsky Eric D, Gelir Ethem, Gelir Seda, Lui Hui, Kattash Maan, DeMayo Francesco J, Shenaq Saleh M, Schwartz Robert J
Michael E. Debakey Department of Surgery, Division of Plastic Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
FASEB J. 2003 Jan;17(1):53-5. doi: 10.1096/fj.02-0183fje. Epub 2002 Nov 1.
Currently, there is no known medical treatment that hastens the repair of damaged nerve and muscle. Using IGF-1 transgenic mice that specifically express human recombinant IGF-1 in skeletal muscle, we test the hypotheses that targeted gene expression of IGF-1 in skeletal muscle enhances motor nerve regeneration after a nerve crush injury. The IGF-1 transgene affects the initiation of the muscle repair process after nerve injury as shown by increased activation of SCA-1positive myogenic stem cells. Increased satellite cell differentiation and proliferation are observed in IGF-1 transgenic mice, shown by increased expression of Cyclin D1, MyoD, and myogenin. Expression of myogenin and nicotinic acetylcholine receptor subunits, initially increased in both wild-type and IGF-1 transgenic mice, are restored to normal levels at a faster rate in IGF-1 transgenic mice, which indicates a rescue of nerve-evoked muscle activity. Expression of the IGF-1 transgene in skeletal muscle results in accelerated recovery of saltatory nerve conduction, increased innervation as detected by neurofilament expression, and faster recovery of muscle mass. These studies demonstrate that local expression of IGF-1 augments the repair of injured nerve and muscle.
目前，尚无已知的医学治疗方法能够加速受损神经和肌肉的修复。我们利用在骨骼肌中特异性表达人重组胰岛素样生长因子-1（IGF-1）的IGF-1转基因小鼠，来检验以下假设：骨骼肌中IGF-1的靶向基因表达可增强神经挤压伤后的运动神经再生。IGF-1转基因影响神经损伤后肌肉修复过程的启动，这表现为SCA-1阳性肌源性干细胞的激活增加。在IGF-1转基因小鼠中观察到卫星细胞分化和增殖增加，这表现为细胞周期蛋白D1、肌分化抗原（MyoD）和肌细胞生成素的表达增加。肌细胞生成素和烟碱型乙酰胆碱受体亚基的表达最初在野生型和IGF-1转基因小鼠中均增加，但在IGF-1转基因小鼠中恢复到正常水平的速度更快，这表明神经诱发的肌肉活动得到了挽救。骨骼肌中IGF-1转基因的表达导致跳跃性神经传导加速恢复、通过神经丝表达检测到的神经支配增加以及肌肉质量更快恢复。这些研究表明，IGF-1的局部表达可增强受损神经和肌肉的修复。
