The Nociceptin/Orphanin FQ System Is Modulated in Patients Admitted to ICU with Sepsis and after Cardiopulmonary Bypass

Background And ObjectivesNociceptin/Orphanin FQ (N/OFQ) is a non-classical endogenous opioid peptide that modulates immune function invitro. Its importance in inflammation and human sepsis is unknown. The objectives of this study were to determine the relationship between N/OFQ, transcripts for its precursor (pre-pro-N/OFQ [ppNOC]) and receptor (NOP), inflammatory markers and clinical outcomes in patients undergoing cardiopulmonary bypass and with sepsis. MethodsA prospective observational cohort study of 82 patients admitted to Intensive Care (ICU) with sepsis and 40 patients undergoing cardiac surgery under cardiopulmonary bypass (as a model of systemic inflammation). Sixty three healthy volunteers, matched by age and sex to the patients with sepsis were also studied. Clinical and laboratory details were recorded. Polymorph ppNOC and NOP receptor mRNA were determined using quantitative PCR. Plasma N/OFQ was determined using ELISA and cytokines (TNF- α, IL-8, IL-10) measured using radioimmunoassay. Data from patients undergoing cardiac surgery were recorded before, 3 and 24 hours after cardiopulmonary bypass. ICU patients with sepsis were assessed on Days 1 and 2 of ICU admission, and after clinical recovery. Main ResultsPlasma N/OFQ concentrations increased (p ConclusionsThe N/OFQ system is modulated in ICU patients with sepsis with similar but reduced changes after cardiac surgery under cardiopulmonary bypass. Further studies are required to clarify the role of the N/OFQ system in inflammation and sepsis, and the mechanisms involved.研究背景与目的 伤害感受肽/孤啡肽FQ（Nociceptin/Orphanin FQ，N/OFQ）是一种非经典内源性阿片肽，在体外可调节免疫功能。目前其在炎症及人类脓毒症中的作用尚不明确。本研究旨在明确N/OFQ、其前体（pre-pro-N/OFQ，ppNOC）及受体（NOP）的转录本、炎症标志物与临床结局之间的关联，研究对象为接受体外循环手术的脓毒症患者。 研究方法 本研究为前瞻性观察队列研究，纳入82例因脓毒症入住重症监护病房（Intensive Care Unit，ICU）的患者，以及40例接受体外循环下心脏手术的患者（以该手术作为全身炎症反应的模型）。此外，还纳入63名年龄与性别与脓毒症患者相匹配的健康志愿者。 研究人员记录了所有受试者的临床与实验室相关资料。采用定量PCR（quantitative PCR）检测ppNOC基因多态性及NOP受体mRNA水平；采用酶联免疫吸附试验（ELISA）检测血浆N/OFQ水平；采用放射免疫分析法检测细胞因子TNF-α、IL-8及IL-10的含量。 对于接受心脏手术的患者，分别于体外循环前、体外循环后3小时及24小时采集相关数据；脓毒症ICU患者则于入住ICU的第1、2天以及临床康复后进行评估。 主要研究结果 血浆N/OFQ浓度升高（p[原文统计内容缺失]） 研究结论 N/OFQ系统在脓毒症重症监护病房患者体内存在调节异常，而接受体外循环心脏手术患者的该系统变化虽趋势相似，但程度较轻。未来仍需开展进一步研究，以阐明N/OFQ系统在炎症及脓毒症中的作用及其相关机制。