Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka Suita, Osaka, 565-0871, Japan.
Laboratory of Nano-Bio Probes, RIKEN Quantitative Biology Center, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan.
Sci Rep. 2017 Sep 25;7(1):12255. doi: 10.1038/s41598-017-12065-4.
Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.
挤压伤患者常伴有全身炎症反应综合征，进而导致多器官功能衰竭。晚期糖基化终产物受体（RAGE）作为一种模式识别受体，可调节炎症反应。我们评估了抗 RAGE 抗体在挤压伤模型中的作用。通过 3.0kg 的砝码对大鼠双侧后肢施加压力 6 小时，然后释放。动物随机分为假手术（RAGE-Sh）组、挤压（RAGE-Ctrl）组或抗 RAGE 抗体治疗挤压伤（RAGE-Tx）组。在释放压力后 3、6 和 24 小时采集样本。在 RAGE-Ctrl 组，肺部荧光免疫染色显示 3 小时时 RAGE 表达上调。血清可溶性 RAGE（sRAGE）水平，反映全身组织中 RAGE 的表达量，在 6 小时时增加。血清白细胞介素 6（IL-6；全身性炎症标志物）在 3 小时时立即增加。组织学分析显示在 6 和 24 小时时肺部损伤。在释放压迫前给予抗 RAGE 抗体可抑制肺肺泡中 RAGE 的上调表达，抑制 RAGE 相关介质 sRAGE 和 IL6，减轻肺损伤并提高 7 天的存活率。总之，我们的研究结果表明，在释放压迫前使用抗 RAGE 抗体与挤压伤后有利的预后相关。
