Pan Ming, Choudry Haroon A, Epler Mark J, Meng Qinghe, Karinch Anne, Lin Chengmao, Souba Wiley
Department of Surgery at the Penn State College of Medicine and the Hershey Medical Center, Hershey, PA 17033, USA.
J Nutr. 2004 Oct;134(10 Suppl):2826S-2829S; discussion 2853S. doi: 10.1093/jn/134.10.2826S.
Arginine appears to be a semiessential amino acid in humans during critical illness. Catabolic disease states such as sepsis, injury, and cancer cause an increase in arginine utilization, which exceeds body production, leading to arginine depletion. This is aggravated by the reduced nutrient intake that is associated with critical illness. Arginine depletion may have negative consequences on tissue function under these circumstances. Nutritional regimens containing arginine have been shown to improve nitrogen balance and lymphocyte function, and stimulate arginine transport in the liver. We have studied the effects of stress mediators on arginine transport in vascular endothelium, liver, and gut epithelium. In vascular endothelium, endotoxin stimulates arginine uptake, an effect that is mediated by the cytokine tumor necrosis factor-alpha (TNF-alpha) and by the cyclo-oxygenase pathway. This TNF-alpha stimulation involves the activation of intracellular protein kinase C (PKC). A significant increase in hepatic arginine transport activity also occurs following burn injury and in rats with progressive malignant disease. Surgical removal of the growing tumor results in a normalization of the accelerated hepatic arginine transport within days. Chronic metabolic acidosis and sepsis individually augment intestinal arginine transport in rats and Caco-2 cell culture. PKC and mitogen-activated protein kinases are involved in mediating the sepsis/acidosis stimulation of arginine transport. Understanding the regulation of plasma membrane arginine transport will enhance our knowledge of nutrition and metabolism in seriously ill patients and may lead to the design of improved nutritional support formulas.
在危重病期间，精氨酸对人类而言似乎是一种半必需氨基酸。分解代谢性疾病状态，如脓毒症、损伤和癌症，会导致精氨酸利用率增加，超过身体的合成能力，从而导致精氨酸耗竭。危重病相关的营养摄入减少会加剧这种情况。在这些情况下，精氨酸耗竭可能会对组织功能产生负面影响。含精氨酸的营养方案已被证明可改善氮平衡和淋巴细胞功能，并刺激肝脏中的精氨酸转运。我们研究了应激介质对血管内皮、肝脏和肠道上皮细胞中精氨酸转运的影响。在血管内皮中，内毒素刺激精氨酸摄取，这种作用由细胞因子肿瘤坏死因子-α（TNF-α）和环氧化酶途径介导。这种TNF-α刺激涉及细胞内蛋白激酶C（PKC）的激活。烧伤后以及患有进行性恶性疾病的大鼠肝脏中，精氨酸转运活性也会显著增加。手术切除生长中的肿瘤会在数天内使加速的肝脏精氨酸转运恢复正常。慢性代谢性酸中毒和脓毒症分别会增强大鼠和Caco-2细胞培养中的肠道精氨酸转运。PKC和丝裂原活化蛋白激酶参与介导脓毒症/酸中毒对精氨酸转运的刺激作用。了解质膜精氨酸转运的调节将增进我们对重症患者营养和代谢的认识，并可能有助于设计出改进的营养支持配方。
