谷氨酰胺双肽在临床营养中的运用

Dipeptides in clinical nutrition

A)What should be known about supplemental glutamine-(dipeptides)?In numerous controlled clinical trials it could be convincingly demonstrated that supplemental glutamine-(dipeptide) nutrition was associated with improved nitrogen balance and mood;increased protein synthesis and lymphocyte count (total and subpopulation);maintained intestinal function,intracellular muscle free glutamine pool,gut permeability and function;reduced 3MeHis excretion,morbidity,length of hospital stay and sepsis frequency.A current European multi center study with ala-gln provides convincing evidence that the clinical use of glutamine dipeptide spares nitrogen and shortens length of hospital stay as compared with the controls.The infusion of the glutamine containing dipeptide solution was free of any side effects, and recovery was normal for each patient.Provision of glutamine-（dipeptide） should be considered as a replacement of a deficiency rather than a supplement.This implies that the beneficial effects observed are due to a correction of disadvantages produced by an inadequacy of conventional nutrition.B)What is new in glutamine(dipeptide)research?(1)It is purposed that tiessue glutathione synthesis is a crucial factor in causing reversal of the clinical,biochemical signs of critical illness,a condition associated with decreased glutathione status.Indeed,the decreased ratio GSH/GSSG suggests oxidative stress in the tissues.In the uture,glutamine containing dipeptides will certainly serve as a means to maintain and/or restore tissur glutathione concentrations.(2)Modification of the endogenous inflammatory response:attenuation of the elaboration of pro-inflammatory mediators,upregulation of antiinflammatory factors,improved immune response.Studies are in progress showing that supplemental glutamine containing dipeptides decrease cytotoxicity and the synthesis of TNFα and IL8 while they enhance the ability to express the anti-inflammatory IL10.An encouraging perspective is the novel finding that provision of alanyl-glutamine promotes the synthesis of cysteinyl-leukotrienes and that the capacity to generate cysteinylleukotrienes is associated with the outcome,serving as a biomarker for survival.The question might be raised,whether the combined deficiency of glutathione and glutamine is intrinsically related to the leukotriene synthesizing capacity of the sick cell.These factors might be mediated through enhanced synthesis of glutathione.(3)Growth factors-glutamine-(dipeptide) interaction.represents a new strategy to enhance the efficacy of glutamine-(dipeptide) nutrition.Growth factors to consider:human growth hormone,insulin-like growth factor I and epidermal growth factor.(4)A novel method enabling accurate measurements of protein-bound glutamine in protein or peptide-based enteral diets.The knowledge of glutamine content in various proteins facilitates revision of tissue/organ glutamine kinetics.(C)How to use glutamine (dipeptides) in routine clinicial setting?Major questions:which patients,when to start,how much,how long to administer;which route of administration,how to monitor efficacy?