Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats
Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats
复制标题
他莫昔芬减轻大鼠脊髓损伤后炎症介导的损伤并改善功能结果
DOI：
10.1111/j.1471-4159.2009.06077.x
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发表时间：
2009-06-01
影响因子：
4.7
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Tian, Dai-Shi;Liu, Jun-Li;Wang, Wei
已经发现他莫昔芬在短暂性和永久性实验性缺血性中风中具有神经保护作用。然而，目前尚不清楚这种药物是否在脊髓损伤（SCI）后显示出类似的有益作用，以及其潜在的机制是什么。在这项研究中，我们研究了他莫昔芬治疗在减轻SCI诱导的病理学的疗效。在脊髓挫伤大鼠中测定血脊髓屏障（BSCB）通透性、组织水肿形成、小胶质细胞活化、神经元细胞死亡和髓鞘丢失。结果显示，三苯氧胺在伤后30 min给药，可显著降低小胶质细胞活化诱导的白细胞介素-1 β（IL-1 β）产生，减轻伊文思蓝渗漏量和水肿形成。此外，他莫昔芬治疗明显减少了SCI后凋亡神经元的数量。还发现在损伤后第3天髓磷脂损失和髓磷脂相关轴突生长抑制剂产生的增加显著减弱。此外，用他莫昔芬治疗的大鼠在SCI后的运动评定量表上的得分远高于载体治疗的大鼠，这表明SCI后的功能结果得到改善。总之，这些结果表明，他莫昔芬提供神经保护作用的SCI相关的病理和残疾的治疗，因此是一个潜在的神经保护剂的人类脊髓损伤治疗。
Tamoxifen has been found to be neuroprotective in both transient and permanent experimental ischemic stroke. However, it remains unknown whether this agent shows a similar beneficial effect after spinal cord injury (SCI), and what are its underlying mechanisms. In this study, we investigated the efficacy of tamoxifen treatment in attenuating SCI-induced pathology. Blood-spinal cord barrier (BSCB) permeability, tissue edema formation, microglial activation, neuronal cell death and myelin loss were determined in rats subjected to spinal cord contusion. The results showed that tamoxifen, administered at 30 min post-injury, significantly decreased interleukin-1 beta (IL-1 beta) production induced by microglial activation, alleviated the amount of Evans blue leakage and edema formation. In addition, tamoxifen treatment clearly reduced the number of apoptotic neurons post-SCI. The myelin loss and the increase in production of myelin-associated axonal growth inhibitors were also found to be significantly attenuated at day 3 post-injury. Furthermore, rats treated with tamoxifen scored much higher on the locomotor rating scale after SCI than did vehicle-treated rats, suggesting improved functional outcome after SCI. Together, these results demonstrate that tamoxifen provides neuroprotective effects for treatment of SCI-related pathology and disability, and is therefore a potential neuroprotectant for human spinal cord injury therapy.