PDF(Pubmed)
Abstract：
Although a wide variety of mechanisms take part in the secondary injury phase of spinal cord injury (SCI), inflammation is the most important factor implicated in the sequelae after SCI. Being central to the inflammation reaction, macrophages and their polarization are a topic that has garnered wide interest in the studies of SCI secondary injury. The glucagon-like peptide 1 (GLP-1) receptor agonist exenatide has been shown to enhance the endoplasmic reticulum stress response and improve motor function recovery after spinal cord injury (SCI). Since exenatide has also been reported to induce the production of M2 cells in models of cerebral infarction and neurodegenerative diseases, this study was conducted to examine the effects of exenatide administration on the inflammation process that ensues after spinal cord injury. In a rat contusion model of spinal cord injury, the exenatide group received a subcutaneous injection of 10 μg exenatide immediately after injury while those in the control group received 1 mL of phosphate-buffered saline. Quantitative RT-PCR and immunohistochemical staining were used to evaluate the effects of exenatide administration on the macrophages infiltrating the injured spinal cord, especially with regard to macrophage M1 and M2 profiles. The changes in hind limb motor function were assessed based on Basso, Beattie, Bresnahan locomotor rating scale (BBB scale) scores. The improvement in BBB scale scores was significantly higher in the exenatide group from day 7 after injury and onwards. Quantitative RT-PCR revealed an increase in the expression of M2 markers and anti-inflammatory interleukins in the exenatide group that was accompanied by a decrease in the expression of M1 markers and inflammatory cytokines. Immunohistochemical staining showed no significant difference in M1 macrophage numbers between the two groups, but a significantly higher number of M2 macrophages was observed in the exenatide group on day 3 after injury. Our findings suggest that exenatide administration promoted the number of M2-phenotype macrophages after SCI, which may have led to the observed improvement in hind limb motor function in a rat model of SCI.
摘要：
尽管多种机制参与了脊髓损伤（SCI）的继发性损伤阶段，炎症是影响SCI后后遗症的最重要因素。是炎症反应的核心，巨噬细胞及其极化是SCI继发性损伤研究中引起广泛兴趣的课题。胰高血糖素样肽1（GLP-1）受体激动剂艾塞那肽已被证明可增强内质网应激反应并改善脊髓损伤（SCI）后的运动功能恢复。由于艾塞那肽也被报道在脑梗塞和神经退行性疾病模型中诱导M2细胞的产生，本研究旨在研究艾塞那肽对脊髓损伤后炎症过程的影响.在大鼠脊髓损伤挫伤模型中,艾塞那肽组受伤后立即接受皮下注射10μg艾塞那肽,而对照组接受1mL磷酸盐缓冲盐水.采用定量RT-PCR和免疫组化染色评价艾塞那肽对脊髓损伤巨噬细胞浸润的影响,特别是关于巨噬细胞M1和M2谱。后肢运动功能的变化是基于Basso，Beattie,Bresnahan运动能力评定量表(BBB量表)评分。从损伤后第7天开始，艾塞那肽组的BBB量表评分改善明显更高。定量RT-PCR显示，艾塞那肽组M2标志物和抗炎白介素的表达增加，同时M1标志物和炎性细胞因子的表达降低。免疫组化染色显示M1巨噬细胞数在两组间无显著差异,但在损伤后第3天,艾塞那肽组的M2巨噬细胞数量显著增加.我们的发现表明，艾塞那肽给药可促进SCI后M2表型巨噬细胞的数量，这可能导致SCI大鼠模型后肢运动功能的改善。
