Immune-enhancing enteral nutrients differentially modulate the early proinflammatory transcription factors mediating gut ischemia/reperfusion.
Immune-enhancing enteral nutrients differentially modulate the early proinflammatory transcription factors mediating gut ischemia/reperfusion.
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DOI：
10.1097/01.ta.0000153937.04932.59
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发表时间：
2005-03
期刊：
影响因子：
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通讯作者：
N. Sato;F. Moore;M.A. Smith;L. Zou;S. Moore-Olufemi;S. Schultz;R. Kozar
中科院分区：
文献类型：
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作者：
N. Sato;F. Moore;M.A. Smith;L. Zou;S. Moore-Olufemi;S. Schultz;R. Kozar
背景：最近的报道表明，富含精氨酸的肠内饮食可能通过增加炎症而有害。这与我们的肠缺血/再灌注(I/R)模型是一致的，在该模型中，精氨酸诱导促炎介质诱导型一氧化氮合酶，导致损伤和炎症，而谷氨酰胺具有保护作用。我们现在假设精氨酸和谷氨酰胺对肠I/R激活的早期促炎转录因子有不同的调节作用。方法在开腹手术中，空肠囊中充满60 mmol/L的谷氨酰胺、精氨酸或等渗对照，然后阻断肠系膜上动脉60min，再灌注6h，并与假手术组进行比较。用凝胶迁移率改变分析法检测空肠组织中核因子-kappaB和激活蛋白-1(AP-1)的表达，用超移位方法检测c-jun和c-fos(AP-1家族)的表达。结果肠I/R可激活NF-kappaB和AP-1，精氨酸和谷氨酰胺对NF-kappaB无明显影响，而AP-1的表达(c-jun，而不是c-fos)在精氨酸作用下显著增强，而谷氨酰胺作用明显减弱。结论精氨酸可促进早期炎性转录因子AP-1的表达，但不能促进核因子-kappaB的表达。这代表了一种新的机制，通过这种机制，精氨酸在给危重患者使用时可能是有害的。
BACKGROUND Recent reports suggest that enteral diets enriched with arginine may be harmful by enhancing inflammation. This is consistent with our gut ischemia/reperfusion (I/R) model in which arginine induced the proinflammatory mediator inducible nitric oxide synthase and resulted in injury and inflammation whereas glutamine was protective. We now hypothesize that arginine and glutamine differentially modulate the early proinflammatory transcription factors activated by gut I/R. METHODS At laparotomy, jejunal sacs were filled with either 60 mmol/L glutamine, arginine, or an iso-osmotic control followed by 60 minutes of superior mesenteric artery occlusion and 6 hours of reperfusion and compared with shams. Jejunum was harvested for nuclear factor (NF)-kappaB and activator protein-1 (AP-1) measured by electrophoretic mobility shift assay and c-jun and c-fos (AP-1 family) by supershift. RESULTS Both NF-kappaB and AP-1 were activated by gut I/R. Arginine and glutamine had no differential effect on NF-kappaB, whereas AP-1 expression (c-jun but not c-fos) was markedly enhanced by arginine and significantly lessened by glutamine. CONCLUSION Arginine enhanced expression of the early proinflammatory transcription factor AP-1 but not NF-kappaB. This represents a novel mechanism by which arginine may be harmful when administered to critically ill patients.