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

合成糖皮质激素甲泼尼龙琥珀酸钠（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，其有益作用的机制尚不完全清楚。实验证据表明，MPSS可能在一定程度上对脊髓损伤有神经保护作用。另一方面，神经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，为神经系统疾病的治疗提供了希望。在这项研究中，我们研究了MPSS对损伤脊髓组织中GDNF mRNA和蛋白产生的影响。8周龄雄性Sprague-Dawley大鼠于T9时切除椎板，投下10g体重诱导脊髓损伤。脊髓损伤后大鼠静脉注射MPSS 30mg/kg，并在适当的时间点对动物进行分析。免疫组化法检测各组GDNF蛋白表达水平，RT-PCR法检测各组GDNF mRNA表达水平。脊髓损伤增强了GDNF mRNA的表达和蛋白的生成。损伤后12h达到最大值。而在MPSS处理组，GDNF mRNA的诱导作用被消除，GDNF蛋白产量的增加减弱。结果表明，MPSS在脊髓损伤早期抑制GDNF基因表达和蛋白合成。考虑到MPSS减轻了创伤后伴随水肿和肿胀的炎症级联反应，加重了神经元损伤，因此脊髓损伤早期GDNF的升高可能不利于脊髓神经元的存活和恢复。

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.