Identification and analysis of genes induced in peripheral nerve after axotomy using cDNA microarrays

众所周知，损伤的外周轴突再生成功，而不是中央轴突。然而，完全的功能恢复很少实现。为了解决这个问题，在先前的研究中，我们使用cDNA微阵列技术确定了周围神经切断后诱导的500个基因。这个项目的目的是分析这些基因的精确功能。主要研究结果如下。1.在p21基因敲除小鼠上建立坐骨神经损伤模型，发现p21是一种有效的Rho激酶抑制剂，可以调节再生轴突的径向生长，从而促进功能恢复。神经丝重链亚基的过度磷酸化被认为是p21基因敲除小鼠径向生长受损的主要原因。2.将临床应用的Rho相关激酶抑制剂盐酸法舒地尔应用于大鼠腓神经损伤模型。损伤后，法舒地尔治疗组动物的功能恢复速度明显快于对照组。3.用原位杂交法检测轴突引导信号分子Sit-Robo的mRNA表达变化。大鼠面神经切断后，面神经核内Slit1表达上调，Slit2表达下调。相反，这两种表达在远端雪旺细胞中都上调。

It is generally known that injured peripheral axons regenerate successfully as oppose to central axons. However, complete functional recovery is rarely achieved. To solve this problem, we identified 500 genes induced in peripheral nerve after axotomy using cDNA microarrays in a previous study. The purpose of this project was to analyze the precise function of these genes. The main findings were as follows. 1. Sciatic nerve injury models were created on the p21 knock out mice and it was found that p21, which is a potent Rho kinase inhibitor, regulates radial growth of regenerating axons, thereby promoting functional recovery. Hyperphosphorylation of the neurofilament heavy chain subunits was considered to be the main reason for the impaired radial growth in the p21 knock out mice. 2. The clinically tested Rho-associated kinase inhibitor fasudil hydrochloride was applied to rat peroneal nerve injury models. After injury, significantly accelerated functional recovery was achieved in the fasudil treated animals as compared with control animals. 3. The mRNA expression changes of Slit-Robo signal molecules, known as axonal guidance cues, were examined using in situ hybridization. After transection of a rat facial nerve, up-regulation of slitl expression and down-regulation of slit2 expression were found in the facial nucleus. In contrast, both expressions were up-regulated in the distal Schwann cells.