Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia.
Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia.
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Interleukin-6 疗法可改善缺血后的肠道恢复。
DOI：
10.1016/j.jss.2019.02.001
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Markel,TroyA
中科院分区：
文献类型：
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作者：
TeWinkel,JanP;Drucker,NatalieA;Morocho,BryantS;Shelley,WChristopher;Markel,TroyA
背景白细胞介素-6（IL-6）具有促炎和抗炎双重作用，但其对肠缺血后恢复的影响尚不清楚。我们假设，肠缺血后IL 6的管理将改善肠系膜灌注和mucosal injuries.MethodsAdult雄性C57 Bl 6 J小鼠麻醉，并进行剖腹手术。通过激光多普勒成像评估基线肠灌注。通过暂时阻断上级肠系膜动脉诱导肠缺血60分钟。局部缺血后，在闭合前腹膜内给予治疗（媒介物：250 μL磷酸盐缓冲盐水，IL 6低剂量（20 ng）、IL 6中等剂量（200 ng）或IL 6高剂量（2 μg））。使动物恢复24小时，重新麻醉，并重新评估其肠系膜灌注。灌注表示为基线的百分比。然后处死动物，取出肠进行组织学分析。将单独的冷冻样本均质化，并通过ELISA分析血管内皮生长因子（VEGF）和干扰素γ诱导蛋白10。结果IL 6仅在低剂量组增加肠系膜灌注，而在低、中剂量组均改善缺血后粘膜损伤评分。当使用高剂量IL 6时，灌注或组织学没有差异。肠VEGF在低剂量IL 6组中高于媒介物，而IP-10水平在低和中剂量组中低于媒介物。没有显着差异相比，车辆在肠道VEGF和IP-10与高剂量IL 6 therapy. ConclusionsLowers剂量的IL 6可能作为有效的治疗，以减少缺血后肠损伤。在广泛临床应用之前，需要进一步的研究来阐明下游机制。
BackgroundInterleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury.MethodsAdult male C57Bl6J mice were anesthetized, and a laparotomy was performed. Baseline intestinal perfusion was assessed by laser Doppler imaging. Intestinal ischemia was induced for 60 min by temporarily occluding the superior mesenteric artery. After ischemia, treatments were administered intraperitoneally before closure (Vehicle: 250 μL phosphate-buffered-saline, IL6 low dose (20 ng), IL6 medium dose (200 ng), or IL6 high dose (2 μg)). Animals were allowed to recover for 24 h, were reanesthetized, and their mesenteric perfusion was reassessed. Perfusion was expressed as percentage of baseline. Animals were then sacrificed, and the intestines were explanted for histological analysis. Separate frozen samples were homogenized and analyzed by ELISA for vascular endothelial growth factor (VEGF) and interferon gamma-induced protein 10.ResultsIL6 increased mesenteric perfusion in low dose groups only, whereas it improved postischemic mucosal injury scores in both low and medium dose groups. No differences in perfusion or histology were seen when high dose IL6 was utilized. Intestinal VEGF was higher in the low dose IL6 group compared to vehicle, whereas IP-10 levels were lower in low and medium dose groups compared to vehicle. No differences were noted compared to vehicle in intestinal VEGF and IP-10 with high dose IL6 therapy.ConclusionsLower doses of IL6 may serve as effective therapy to decrease intestinal injury after ischemia. Further studies are needed to elucidate the downstream mechanisms before widespread clinical use.