Department of Critital Care Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing 100050, China.
Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing 100050, China.
Clin Immunol. 2021 Feb;223:108660. doi: 10.1016/j.clim.2020.108660. Epub 2020 Dec 25.
The study aimed to understand the molecular mechanisms that might lead to differences in the glucocorticoid response during sepsis.
Patients diagnosed with sepsis (n = 198) and 40 healthy controls were enrolled. Glucocorticoid receptor (GR) expression in circulating leukocytes and plasma levels of adrenocorticotropic hormone and cortisol on days 1 and 7 were measured in all participants. Expression profiling of 16 genes associated with GR expression in peripheral blood mononuclear cells (PBMCs) in 12 healthy controls and 26 patients with sepsis was performed by PCR.
Cortisol levels were higher in patients with sepsis than in healthy controls on day 1 after admission and recovered to normal levels by day 7. GR expression was gradually downregulated in leukocyte subsets. Non-survivors showed lower GR and higher cortisol levels than survivors. GRα expression was lower in patients with sepsis than in controls, whereas GRβ showed the opposite trend. MicroRNAs related to GR resistance and suppression were altered in PBMCs during sepsis.
Patients with sepsis showed upregulated plasma cortisol levels along with downregulated GR expression on various leukocyte subtypes, portending poor cortisol response and outcome. Changes in GR-regulatory miRNAs may be responsible for GR low expression.
本研究旨在探讨导致脓毒症患者糖皮质激素反应存在差异的分子机制。
纳入 198 例脓毒症患者和 40 名健康对照者。所有参与者均在入院第 1 天和第 7 天检测循环白细胞中的糖皮质激素受体（GR）表达水平以及血浆促肾上腺皮质激素和皮质醇水平。对 12 名健康对照者和 26 名脓毒症患者的外周血单个核细胞（PBMCs）中与 GR 表达相关的 16 个基因进行 PCR 表达谱分析。
与健康对照组相比，入院第 1 天脓毒症患者的皮质醇水平更高，第 7 天恢复正常。白细胞亚群中的 GR 表达逐渐下调。与幸存者相比，非幸存者的 GR 和皮质醇水平更低。脓毒症患者的 GRα 表达低于对照组，而 GRβ 则呈现相反的趋势。脓毒症期间 PBMCs 中的 GR 抵抗和抑制相关 microRNAs 发生改变。
脓毒症患者表现为血浆皮质醇水平升高，各种白细胞亚群中的 GR 表达下调，预示着皮质醇反应不良和预后不良。GR 调节 microRNAs 的变化可能是 GR 低表达的原因。
