Genovese Tiziana, Mazzon Emanuela, Crisafulli Concetta, Esposito Emanuela, Di Paola Rosanna, Muià Carmelo, Di Bella Paolo, Bramanti Placido, Cuzzocrea Salvatore
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.
J Pineal Res. 2007 Sep;43(2):140-53. doi: 10.1111/j.1600-079X.2007.00454.x.
This study investigates the effects of combination therapy with melatonin and dexamethasone on the degree of spinal cord injury caused by the application of vascular clip in mice. Spinal cord injury in mice resulted in severe trauma, characterized by edema, neutrophil infiltration, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and immunoreaction of Bax, Bcl-2, and Fas Ligand). Infiltration of the spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced immuno- histochemical and functional alterations revealed, respectively, by an increased of tumor necrosis factor (TNF)-alpha immunoreactivity, NOS as well as nitrotyrosine and loss of hind leg movement in spinal cord injury (SCI)-operated mice. In contrast, the degree of neutrophil infiltration at different time points, cytokine expression, histologic damage iNOS expression, apoptosis, was markedly reduced in the tissues obtained from SCI-treated mice with the combination therapy, and the motor recovery was also ameliorated. No anti-inflammatory effect was observed in animals treated with melatonin (10 mg/kg) or with dexamethasone (0.025 mg/kg) alone. This study shows that the combination therapy with melatonin and dexamethasone reduces the degree of secondary damage associated with spinal cord injury in mice, and supports the possible use of melatonin in combination with steroids to reduce the dose and the side effects related with the use of steroids for the management of inflammatory disease.
本研究调查了褪黑素与地塞米松联合治疗对小鼠应用血管夹所致脊髓损伤程度的影响。小鼠脊髓损伤导致严重创伤，其特征为水肿、中性粒细胞浸润和细胞凋亡（通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色以及Bax、Bcl-2和Fas配体的免疫反应来测定）。脊髓组织中的中性粒细胞浸润（以髓过氧化物酶活性增加来衡量）与肿瘤坏死因子（TNF）-α免疫反应性增加、一氧化氮合酶（NOS）以及硝基酪氨酸增加所分别揭示的免疫组化和功能改变增强相关，并且与脊髓损伤（SCI）手术小鼠的后腿运动丧失相关。相比之下，在接受联合治疗的SCI处理小鼠所获得的组织中，不同时间点的中性粒细胞浸润程度、细胞因子表达、组织学损伤、诱导型一氧化氮合酶（iNOS）表达、细胞凋亡均显著降低，并且运动恢复也得到改善。单独用褪黑素（10 mg/kg）或地塞米松（0.025 mg/kg）治疗的动物未观察到抗炎作用。本研究表明，褪黑素与地塞米松联合治疗可减轻小鼠脊髓损伤相关的继发性损伤程度，并支持褪黑素与类固醇联合使用以减少类固醇用于治疗炎症性疾病时的剂量及相关副作用的可能性。
