补充大剂量半胱氨酸对红细胞谷胱甘肽的影响：重症新生儿双盲、随机安慰剂对照初步研究

　　背景：本研究旨在明确对炎症性损伤高危新生儿经肠外给予半胱氨酸是否能增加红细胞内还原型谷胱甘肽（GSH）。

　　资料与方法：在该双盲对照研究中，将急性生理学评分＞10且需要机械通气和肠外营养（PN）的新生儿随机经肠外给予半胱氨酸-HCl（CYS组）或经PN给予121mg/kg/d的额外氨基酸（ISO组）≥7天。在该研究的第一周给予6h的[13C2]甘氨酸静脉输注以了解GSH的分解合成速率（FSR-GSH）。

　　结果：CYS组（n=17）和ISO组（n=21）的基线资料相似。两组的红细胞内GSH，谷胱甘肽总浓度，GSH：氧化型GSH（GSSG）以及治疗后的FSR-GSH均没有差异。然而，与ISO组相比，CYS组的GSH和总谷胱甘肽水平（输入天数-基线）显著增加（二者均P=0.02）。调整治疗因素后，患儿体重和红细胞输注率的降低与总谷胱甘肽和GSH水平的降低有关（两者均P＜0.05）。

　　结论：与补充等氮非半胱氨酸对照相比，给予重症新生儿补充大剂量半胱氨酸至少一周可以大大增加GSH水平。在小婴儿和接受输血的小儿中，补充半胱氨酸对GSH的影响不大。半胱氨酸的疗效是有前景的，仍需进一步研究。

JPEN J Parenter Enteral Nutr. 2016;40(2):226-34.

Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double-Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates.

Calkins KL, Sanchez LA, Tseng CH, Faull KF, Yoon AJ, Ryan CM, Le T, Shew SB.

David Geffen School of Medicine, University of California, Los Angeles, California; Mattel Children's Hospital at UCLA, Los Angeles, California.

BACKGROUND: This study's objective was to determine if parenteral cysteine when compared with isonitrogenous noncysteine supplementation increases erythrocyte reduced glutathione (GSH) in neonates at high risk for inflammatory injury.

MATERIAL AND METHODS: Neonates with a score for neonatal acute physiology >10 requiring mechanical ventilation and parenteral nutrition (PN) were randomized in a double-blinded, placebo-controlled study to receive parenteral cysteine-HCl (CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/d for ≥7 days. A 6-hour [(13)C2] glycine IV infusion was administered at study week 1 to determine the fractional synthetic rate of GSH (FSR-GSH).

RESULTS: Baseline characteristics were similar between the CYS (n = 17) and ISO groups (n = 21). Erythrocyte GSH and total glutathione concentrations, GSH:oxidized GSH (GSSG), and FSR-GSH after treatment were not different between groups. However, the CYS group had a larger individual positive change in GSH and total glutathione (infusion day - baseline) compared with the ISO group (P = .02 for each). After adjusting for treatment, a lower enrollment weight and rate of red blood cell transfusion were associated with a decreased change in total glutathione and GSH (P < .05 for each).

CONCLUSION: When compared with isonitrogenous noncysteine supplementation, high-dose cysteine supplementation for at least 1 week in critically ill neonates resulted in a larger and more positive individual change in GSH. Smaller infants and those who received transfused blood demonstrated less effective change in GSH with cysteine supplementation. The benefit of cysteine remains promising and deserves further investigation.

KEYWORDS: antioxidant; chronic lung disease; inflammation; neonates; parenteral nutrition; prematurity; red blood cell

PMID: 25139979

PMCID: PMC4573914

DOI: 10.1177/0148607114546375