Genovese Tiziana, Mazzon Emanuela, Muià Carmelo, Bramanti Placido, De Sarro Angelina, Cuzzocrea Salvatore
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
J Pineal Res. 2005 Apr;38(3):198-208. doi: 10.1111/j.1600-079X.2004.00194.x.
Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. In the present study, we evaluated the effect of melatonin treatment, in a model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with melatonin reduces the development of inflammation and tissue injury events associated with spinal cord trauma.
褪黑素是松果体的主要分泌产物，其作为免疫调节剂的作用已得到充分证实。最近的证据表明，褪黑素是氧自由基和过氧亚硝酸盐的清除剂，在脓毒症休克、失血性休克和炎症中发挥保护作用。在本研究中，我们评估了褪黑素治疗在脊髓损伤（SCI）模型中的效果。通过四级T5 - T8椎板切除术对硬脑膜施加血管夹（50 g力）诱导SCI。大鼠的SCI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缺口末端标记染色测量）。脊髓组织中中性粒细胞的浸润（以髓过氧化物酶活性增加来衡量）与脂质过氧化增强（丙二醛组织水平升高）相关。免疫组织化学检查显示脊髓组织中硝基酪氨酸和聚（ADP - 核糖）（PAR）的免疫反应性显著增加。相比之下，在用褪黑素治疗的大鼠（50 mg/kg腹腔注射，在SCI前30分钟、SCI后30分钟、6小时、12小时和24小时）获得的脊髓组织中，（a）脊髓炎症和组织损伤程度（组织学评分）、（b）硝基酪氨酸和PAR形成、（c）中性粒细胞浸润和（d）细胞凋亡均显著降低。在另一组实验中，我们清楚地证明褪黑素治疗显著改善了肢体功能的恢复（通过运动恢复评分评估）。综上所述，我们的结果表明，褪黑素治疗可减少与脊髓创伤相关的炎症和组织损伤事件的发生。
