Beneficial effects of thymosin β4 on spinal cord injury in the rat
Beneficial effects of thymosin β4 on spinal cord injury in the rat
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DOI：
10.1016/j.neuropharm.2014.06.004
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发表时间：
2014-10-01
影响因子：
4.7
通讯作者：
Wang, Jian
中科院分区：
文献类型：
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作者：
Cheng, Peng;Kuang, Fang;Wang, Jian
胸腺素β 4（T β 4）具有许多与脊髓损伤（SCI）高度相关的生理功能，包括神经元存活、抗炎、促进伤口修复和血管生成。本研究调查了T β 4在SCI中的治疗价值，重点是其神经保护，抗炎和血管保护特性。大鼠脊髓损伤后30分钟、3天或5天，通过腹腔注射给予T β 4或生理盐水对照。采用Basso-Beattie-Bresnahan量表和足迹分析测试运动恢复。所有行为评估均在T β 4治疗后显著改善。损伤后7天的组织学检查显示，与盐水处理的对照组相比，T β 4处理的动物中存活的神经元和少突胶质细胞的数量显著增加。髓鞘碱性蛋白（成熟少突胶质细胞的标志物）的水平在T β 4治疗的大鼠中比盐水治疗的对照组高57.8%。与生理盐水处理组相比，T β 4处理组中活化的小胶质细胞/巨噬细胞的标志物ED 1的表达降低了36.9%。与对照组相比，SCI后T β 4治疗还与促炎细胞因子基因表达的显著降低和IL-10 mRNA水平的显著增加相关。此外，与生理盐水处理的对照组相比，T β 4处理的动物中损伤脊髓中星形胶质细胞瘢痕所描绘的病变腔的大小显著减小。鉴于T β 4在临床试验中已知的安全性及其对SCI恢复的有益作用，这项研究的结果表明T β 4是人类SCI治疗的良好候选者。(C)2014爱思唯尔有限公司版权所有。
Thymosin beta 4 (T beta 4) has many physiological functions that are highly relevant to spinal cord injury (SCI), including neuronal survival, anti-inflammation, wound repair promotion, and angiogenesis. The present study investigated the therapeutic value of T beta 4 in SCI, with a focus on its neuroprotective, anti-inflammatory, and vasculoprotective properties. T beta 4 or a saline control was administered by intraperitoneal injection 30 min, 3 days, or 5 days after SCI with mild compression in rat. Locomotor recovery was tested with the Basso-Beattie-Bresnahan scale and a footprint analysis. All behavioral assessments were markedly improved with T beta 4 treatment. Histological examination at 7 days post injury showed that the numbers of surviving neurons and oligodendrocytes were significantly increased in T beta 4-treated animals compared to saline-treated controls. Levels of myelin basic protein, a marker of mature oligodendrocytes, in T beta 4-treated rats were 57.8% greater than those in saline-treated controls. The expression of ED1, a marker of activated microglia/macrophages, was reduced by 36.9% in the T beta 4-treated group compared to that of the saline-treated group. T beta 4 treatment after SCI was also associated with a significant decrease in pro-inflammatory cytokine gene expression and a significant increase in the mRNA levels of IL-10 compared to the control. Moreover, the size of lesion cavity delineated by astrocyte scar in the injured spinal cord was markedly reduced in T beta 4-treated animals compared to saline-treated controls. Given the known safety of T beta 4 in clinical trials and its beneficial effects on SCI recovery, the results of this study suggested that T beta 4 is a good candidate for SCI treatment in humans. (C) 2014 Elsevier Ltd. All rights reserved.