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[谷氨酰胺:对免疫系统、蛋白质平衡及肠道功能的影响]

[Glutamine: effects on the immune system, protein balance and intestinal functions].

作者信息

Roth E, Spittler A, Oehler R

机构信息

Chirurgisches Forschungslaboratorium, Universitätsklinik für Chirurgie, Allgemeines Krankenhaus, Wien.

出版信息

Wien Klin Wochenschr. 1996;108(21):669-76.

PMID:9045524
Abstract

Glutamine is the most abundant free amino acid of the human body. In catabolic stress situations such as after operations, trauma and during sepsis the enhanced transport of glutamine to splanchnic organs and to blood cells results in an intracellular depletion of glutamine in skeletal muscle. Glutamine is an important metabolic substrate for cells cultivated under in vitro conditions and is a precursor for purines, pyrimidines and phospholipids. Increasing evidence suggests that glutamine is a crucial substrate for immunocompetent cells. Glutamine depletion in the cultivation medium decreases the mitogen-inducible proliferation of lymphocytes, possibly by arresting the cells in the G0-G1 phase of the cell cycle. Glutamine depletion in lymphocytes prevents the formation of signals necessary for late activation. In monocytes glutamine deprivation downregulates surface antigens responsible for antigen preservation and phagocytosis. Glutamine is a precursor for the synthesis of glutathionine and stimulates the formation of heat-shock proteins. Moreover, there are suggestions that glutamine plays a crucial role in osmotic regulation of cell volume and causes phosphorylation of proteins, both of which may stimulate intracellular protein synthesis. Experimental studies revealed that glutamine deficiency causes a necrotising enterocolitis and increases the mortality of animals subjected to bacterial stress. First clinical studies have demonstrated a decrease in the incidence of infections and a shortening of the hospital stay in patients after bone marrow transplantation by supplementation with glutamine. In critically ill patients parenteral glutamine reduced nitrogen loss and caused a reduction of the mortality rate. In surgical patients glutamine evoked an improvement of several immunological parameters. Moreover, glutamine exerted a trophic effect on the intestinal mucosa, decreased the intestinal permeability and thus may prevent the translocation of bacteria. In conclusion, glutamine is an important metabolic substrate of rapidly proliferating cells, influences the cellular hydration state and has multiple effects on the immune system, on intestinal function and on protein metabolism. In several disease states glutamine may consequently, become an indispensable nutrient, which should be provided exogenously during artificial nutrition.

摘要

谷氨酰胺是人体中含量最丰富的游离氨基酸。在分解代谢应激状态下,如手术后、创伤后以及脓毒症期间,谷氨酰胺向内脏器官和血细胞的转运增强,导致骨骼肌细胞内谷氨酰胺耗竭。谷氨酰胺是体外培养细胞的重要代谢底物,也是嘌呤、嘧啶和磷脂的前体。越来越多的证据表明,谷氨酰胺是免疫活性细胞的关键底物。培养基中谷氨酰胺的耗竭可能通过使细胞停滞于细胞周期的G0-G1期而降低淋巴细胞有丝分裂原诱导的增殖。淋巴细胞中谷氨酰胺的耗竭会阻止晚期激活所需信号的形成。在单核细胞中,谷氨酰胺缺乏会下调负责抗原保存和吞噬作用的表面抗原。谷氨酰胺是合成谷胱甘肽的前体,并刺激热休克蛋白的形成。此外,有迹象表明谷氨酰胺在细胞体积的渗透调节中起关键作用,并导致蛋白质磷酸化,这两者都可能刺激细胞内蛋白质合成。实验研究表明,谷氨酰胺缺乏会导致坏死性小肠结肠炎,并增加遭受细菌应激动物的死亡率。首批临床研究已证明,补充谷氨酰胺可降低骨髓移植患者的感染发生率并缩短住院时间。在重症患者中,肠外补充谷氨酰胺可减少氮损失并降低死亡率。在外科手术患者中,谷氨酰胺可改善多项免疫参数。此外,谷氨酰胺对肠黏膜具有营养作用,可降低肠道通透性,从而可能防止细菌移位。总之,谷氨酰胺是快速增殖细胞的重要代谢底物,影响细胞水合状态,对免疫系统、肠道功能和蛋白质代谢具有多种作用。因此,在几种疾病状态下,谷氨酰胺可能成为不可或缺的营养素,在人工营养期间应外源提供。

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