Clinical application of Cartilage-derived Retinoic Acid-sensitive Protein in Orthopaedic Surgery

人工合成的糖皮质激素甲基强的松龙琥珀酸钠（MPSS）已被临床用于治疗急性脊髓损伤（SCI），以促进神经功能的恢复。然而，其有益作用的机制并不完全清楚。实验证据表明，MPSS可能有助于在一定程度上对SCI的神经保护。另一方面，胶质细胞系衍生的神经营养因子（GDNF）作为一种有效的存活因子，为神经系统疾病提供了治疗前景。本研究观察了MPSS对损伤脊髓组织GDNF mRNA和蛋白表达的影响。8周龄的雄性Sprague-Dawley大鼠在T9时进行椎板切除，并通过降低10 g的重量来诱导SCI。脊髓损伤后大鼠静脉注射MPSS 30 mg/kg，并在适当的时间点进行分析。采用免疫组化法检测GDNF蛋白表达，RT-PCR法检测GDNF mRNA表达。脊髓损伤可促进GDNF mRNA表达和蛋白质合成。伤后12 h达最大值。MPSS处理组GDNF mRNA的表达被抑制，GDNF蛋白的表达增加被抑制。结果表明，MPSS在脊髓损伤早期抑制GDNF基因表达和蛋白质合成。考虑到MPSS可以减少伴随水肿和肿胀的创伤后炎症级联反应，从而加重神经元损伤，因此SCI早期GDNF的升高可能不利于脊髓神经元的生存和恢复。

The synthetic glucocorticosteroid methylprednisolone sodium succinate (MPSS) has been clinically used for the treatment of acute spinal cord injury (SCI) to promote the recovery of neurological functions. However, the mechanism of its beneficial actions is not entirely understood. Experimental evidence suggests that MPSS may contribute to some extent to neuroprotection in SCI. On the other hand, glial cell line derived neurotorophic factor (GDNF) acts as a potent survival factor for several neuronal populations, providing a therapeutic promise for neurological disorders. In this study, we have investigated the effect of MPSS on the production of GDNF mRNA and protein in the injured spinal cord tissues. Male Sprague-Dawley rats, 8 weeks old, were laminectomized at T9 and SCI was induced by dropping a weight of 10g. MPSS, 30mg/kg, was intravenously administrated to the rats after SCI and the animals were analyzed at the appropriate time points. The level of GDNF protein in the tissue was evaluated by immunohistochemistry and the mRNA levels were determined by RT-PCR. The GDNF mRNA expression and protein production were enhanced by SCI. The maximal values were obtained in the 12h after the injury. In MPSS treated group, however, the induction of GDNF mRNA was abolished and the increase of the GDNF protein production was diminished. The results indicated the MPSS repressed the GDNF gene expression and protein synthesis in the early stage after SCI. Considering the fact that MPSS diminishes the post traumatic inflammatory cascades accompanying edema and swelling to worsen the neuronal injury, the elevation of GDNF in the early stage of SCI might be disadvantageous to the survival and recovery of spinal neurons.