Wilmore D W, Smith R J, O'Dwyer S T, Jacobs D O, Ziegler T R, Wang X D
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Surgery. 1988 Nov;104(5):917-23.
The intestinal tract plays a central role in the protein catabolic response after injury and infection. The mucosa utilizes glutamine and thus spares glucose--presumably sparing this essential fuel source for tissues with an obligate glucose requirement. With inadequate nutritional support or prolonged stress, glutamine levels decrease in both the plasma and the tissue pools, which suggests that glutamine deficiency occurs. This is associated in time with atrophy of the gastrointestinal mucosa. This provision of dietary glutamine results in correction of the abnormally low glutamine concentrations and increased cellularity of the gut mucosa. The derangements in the intestinal mucosa associated with starvation, injury, infection, immunosuppression, chemotherapy, lack of enteral feedings, and other stresses are associated with a breakdown in the barrier function of the gut. Both bacteria and their toxins may enter the host from the intestinal lumen. Through interaction with the reticuloendothelial system, cytokines are produced, which stimulate the pituitary-adrenal axis and thus contribute to the stress response. The elaboration of glucocorticoids facilitates proteolysis, thus increasing glutamine release from skeletal muscle for gut repair. Although this homeostatic mechanism appears to aid mucosal repair and support immunologic responses, severe injury or prolonged glutamine deficits do not adequately support intestinal recovery and allow this cycle to become self-perpetuating (Fig 3). Adequate enteral feedings initiated early in the course of a disease appear to maintain adequate gut barrier function. In the frequent circumstance when feeding by this route is inadequate or impossible, glutamine-containing parenteral feedings offer an appropriate alternative therapy for bowel and immunologic support. Glutamine-containing parenteral feedings are associated with increased mucosal cellularity and improved survival after gut injury. Specific hormones also stimulate mucosal growth, and it is anticipated that a combination of hormones and specific nutrients will provide optimal support of the gut mucosa in the severely ill patient.
肠道在损伤和感染后的蛋白质分解代谢反应中起核心作用。肠黏膜利用谷氨酰胺，从而节省葡萄糖——推测是为那些对葡萄糖有绝对需求的组织节省这种必需的燃料来源。在营养支持不足或长期应激的情况下，血浆和组织库中的谷氨酰胺水平都会下降，这表明发生了谷氨酰胺缺乏。这会随着时间的推移导致胃肠道黏膜萎缩。提供膳食谷氨酰胺可纠正异常低的谷氨酰胺浓度，并增加肠黏膜的细胞数量。与饥饿、损伤、感染、免疫抑制、化疗、缺乏肠内喂养及其他应激相关的肠黏膜紊乱与肠道屏障功能的破坏有关。细菌及其毒素都可能从肠腔进入宿主。通过与网状内皮系统相互作用，会产生细胞因子，刺激垂体-肾上腺轴，从而促成应激反应。糖皮质激素的分泌促进蛋白水解，从而增加骨骼肌释放谷氨酰胺用于肠道修复。尽管这种稳态机制似乎有助于黏膜修复并支持免疫反应，但严重损伤或长期谷氨酰胺缺乏并不能充分支持肠道恢复，反而会使这个循环持续下去（图3）。在疾病过程早期开始的充足肠内喂养似乎能维持足够的肠道屏障功能。在通过这种途径喂养不足或不可能的常见情况下，含谷氨酰胺的肠外喂养为肠道和免疫支持提供了一种合适的替代疗法。含谷氨酰胺的肠外喂养与肠黏膜细胞数量增加及肠道损伤后生存率提高有关。特定激素也会刺激黏膜生长，预计激素和特定营养素的组合将为重症患者的肠黏膜提供最佳支持。
