Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.
Emory Critical Care Center, Emory University, Atlanta, GA, USA.
Eur J Clin Nutr. 2018 May;72(5):744-751. doi: 10.1038/s41430-017-0047-0. Epub 2017 Dec 29.
BACKGROUND/OBJECTIVES: Disruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: (1) characterize the plasma and alveolar thiol/disulfide redox pools, (2) examine their associations with alveolar macrophage phagocytosis, and (3) determine the effect of high dose vitamin D on plasma thiol/disulfide redox.
SUBJECTS/METHODS: Subjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14.
Baseline plasma Cys was inversely associated with alveolar PI (ρ = -0.69, P = 0.003), and ECySS was positively associated with PI (ρ = 0.61, P = 0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EGSSG (P < 0.01 for both), with no difference by treatment group. Vitamin D decreased oxidized plasma GSSG to a more normal state (P for group x time = 0.009).
Oxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.
背景/目的：氧化还原平衡的破坏会导致氧化应激，这是危重病患者发病的一个促进因素。本研究旨在：（1）描述血浆和肺泡硫醇/二硫键氧化还原池的特征，（2）研究它们与肺泡巨噬细胞吞噬作用的关系，（3）确定大剂量维生素 D 对血浆硫醇/二硫键氧化还原的影响。
受试者/方法：这是一项双盲随机试验，共纳入 30 名患有危重病且需要通气的成年人，他们接受大剂量（25 万或 50 万 IU）维生素 D 或安慰剂治疗。在基线时，对支气管肺泡灌洗液（BALF）样本进行分析，以确定肺泡吞噬指数（PI）以及谷胱甘肽（GSH）、谷胱甘肽二硫化物（GSSG）、半胱氨酸（Cys）、胱氨酸（CySS）及其各自氧化还原电势（EhGSSG 和 EhCySS）的浓度。在基线和第 7 天及第 14 天评估血浆氧化还原结果。
基线时，血浆 Cys 与肺泡 PI 呈负相关（ρ=-0.69，P=0.003），ECySS 与 PI 呈正相关（ρ=0.61，P=0.01）。随着时间的推移，所有受试者的血浆 GSH 水平升高，EGSSG 降低（两者均 P<0.01），但治疗组之间无差异。维生素 D 降低了氧化的血浆 GSSG 至更正常的状态（组间 x 时间 P=0.009）。
在急性呼吸危重病患者中，氧化应激指标与肺泡巨噬细胞吞噬功能呈正相关。大剂量维生素 D 降低了血浆 GSSG 浓度，这表明维生素 D 可能改善氧化应激环境。
