Hsieh Yu-Lin, Lin Whei-Min, Lue June-Horng, Chang Ming-Fong, Hsieh Sung-Tsang
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Neuropathol Exp Neurol. 2009 Dec;68(12):1269-81. doi: 10.1097/NEN.0b013e3181c17b46.
We assessed the effects of treatment with 4-methylcatechol (4MC), a known inducer of nerve growth factor, on peripheral nerve regeneration by analyzing cutaneous and muscular reinnervation in mice after sciatic nerve crush injury. At 3 months postinjury, the skin innervation index was significantly higher in the 4MC group than the control group (p=0.0002); there was also increased unmyelinated fiber density (p=0.0042) and unmyelinated fibers/Remak bundle (p = 0.001) in sural nerves, indicating unmyelinated nerve fiber regeneration. These changes were accompanied by increases of transcripts for nerve growth factor (p = 0.0026) and glial cell line-derived neurotrophic factor (p=0.03) in the 4MC group. In contrast, muscle innervation indices were similar in both groups and were higher than the skin innervation index (p < 0.0001). The regeneration of myelinated nerve fibers, as assessed by fiber density, diameter and g ratio analyses in sural nerves, and amplitudes of muscle action potential in sciatic nerves, was similar in both groups. Taken together, these data suggest that 4MC specifically promoted the regeneration of unmyelinated nerve fibers and reinnervation of the skin by increasing the expression of nerve growth factor and glial cell line-derived neurotrophic factor.
我们通过分析坐骨神经挤压损伤后小鼠的皮肤和肌肉再支配情况，评估了已知的神经生长因子诱导剂4-甲基邻苯二酚（4MC）治疗对周围神经再生的影响。在损伤后3个月，4MC组的皮肤神经支配指数显著高于对照组（p = 0.0002）；腓肠神经中无髓纤维密度（p = 0.0042）和无髓纤维/雷马克束（p = 0.001）也增加，表明无髓神经纤维再生。这些变化伴随着4MC组中神经生长因子（p = 0.0026）和胶质细胞源性神经营养因子（p = 0.03）转录本的增加。相比之下，两组的肌肉神经支配指数相似，且高于皮肤神经支配指数（p < 0.0001）。通过腓肠神经的纤维密度、直径和g比值分析以及坐骨神经的肌肉动作电位幅度评估的有髓神经纤维再生，在两组中相似。综上所述，这些数据表明4MC通过增加神经生长因子和胶质细胞源性神经营养因子的表达，特异性地促进了无髓神经纤维的再生和皮肤的再支配。
