冷诱导 RNA 结合蛋白衍生肽 C23 减轻小鼠肠缺血再灌注模型中的炎症和组织损伤。
Cold-inducible RNA-binding protein-derived peptide C23 attenuates inflammation and tissue injury in a murine model of intestinal ischemia-reperfusion.
机构信息
Department of Surgery and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York.
Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York.
出版信息
Surgery. 2018 Dec;164(6):1191-1197. doi: 10.1016/j.surg.2018.06.048. Epub 2018 Aug 25.
BACKGROUND
Cold-inducible RNA-binding protein is a novel damage-associated molecular pattern that causes inflammation. C23, a short peptide derived from cold-inducible RNA-binding protein, has been found to have efficacy in blocking cold-inducible RNA-binding protein's activity. We hypothesized that C23 reduces inflammation and tissue injury induced by intestinal ischemia-reperfusion.
METHODS
Male C57BL/6 mice were subjected to 60 minutes of intestinal ischemia by clamping the superior mesenteric artery. Immediately after reperfusion, either normal saline (vehicle) or C23 peptide (8 mg/kg body weight) was injected intraperitoneally. Four hours after reperfusion, blood, intestinal, and lung tissues were collected for analysis of inflammatory and tissue injury parameters.
RESULTS
Cold-inducible RNA-binding protein levels in the intestinal tissues were significantly increased following intestinal ischemia-reperfusion. Histologic examination of the intestine revealed a significant reduction in injury score in the C23 group by 48% as compared with the vehicles after intestinal ischemia-reperfusion. The serum levels of lactate dehydrogenase and aspartate aminotransferase were increased in animals that underwent vehicle-treated intestinal ischemia-reperfusion, whereas C23-treated animals exhibited significant reductions by 48% and 53%, respectively. The serum and intestinal tissue levels of tumor necrosis factor α were elevated in vehicle-treated intestinal ischemia-reperfusion mice but decreased by 72% and 69%, respectively, in C23-treated mice. Interleukin-6 mRNA levels in the lungs were reduced by 86% in the C23-treated group in comparison to the vehicle-treated group after intestinal ischemia-reperfusion. Expression of macrophage inflammatory protein 2 and level of myeloperoxidase activity in the lungs were dramatically increased after intestinal ischemia-reperfusion and significantly reduced by 91% and 25%, respectively, in the C23-treated group.
CONCLUSION
C23 has potential to be developed into a possible therapy for reperfusion injury after mesenteric ischemia and reperfusion.
背景
冷诱导 RNA 结合蛋白是一种新型的损伤相关分子模式，可引起炎症。C23 是一种从冷诱导 RNA 结合蛋白衍生而来的短肽，已被发现具有阻断冷诱导 RNA 结合蛋白活性的作用。我们假设 C23 可减轻肠缺血再灌注引起的炎症和组织损伤。
方法
雄性 C57BL/6 小鼠通过夹闭肠系膜上动脉进行 60 分钟的肠缺血。再灌注后立即腹膜内注射生理盐水（载体）或 C23 肽（8mg/kg 体重）。再灌注后 4 小时，采集血液、肠和肺组织，分析炎症和组织损伤参数。
结果
肠缺血再灌注后肠组织中冷诱导 RNA 结合蛋白水平明显升高。组织学检查显示，与载体组相比，C23 组肠损伤评分显著降低，降低幅度为 48%。接受载体处理的肠缺血再灌注动物的血清乳酸脱氢酶和天冬氨酸转氨酶水平升高，而 C23 处理的动物分别降低 48%和 53%。血清和肠组织肿瘤坏死因子α水平在接受载体处理的肠缺血再灌注小鼠中升高，但在 C23 处理的小鼠中分别降低 72%和 69%。与载体处理组相比，肠缺血再灌注后 C23 处理组肺组织白细胞介素-6mRNA 水平降低 86%。肺组织巨噬细胞炎症蛋白 2 的表达和髓过氧化物酶活性显著增加，C23 处理组分别降低 91%和 25%。
结论
C23 有可能开发成为治疗肠系膜缺血再灌注后再灌注损伤的潜在疗法。
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