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生物钟基因、褪黑素与重症监护病房患者心血管结局之间的相互作用。

Interaction between clock genes, melatonin and cardiovascular outcomes from ICU patients.

作者信息

Jiménez-Pastor Jose M, Morales-Cané Ignacio, Rodríguez-Cortés Francisco J, López-Coleto Luna, Valverde-León Rocío, Arévalo-Buitrago Pedro, Medina-Valverde María J, De la Fuente-Martos Carmen, Acuña-Castroviejo Darío, Meira E Cruz Miguel, Luque Raúl M, Sarmento-Cabral André, López-Soto Pablo J

机构信息

GC31 Group, Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Cordoba, Spain.

Department of Nursing, Pharmacology and Physiotherapy, University of Córdoba, Córdoba, Spain.

出版信息

Intensive Care Med Exp. 2025 Feb 17;13(1):19. doi: 10.1186/s40635-025-00730-2.

Abstract

BACKGROUND

Circadian rhythms, driven by biological clocks, help organisms align their physiological functions with environmental changes, promoting homeostasis. The central clock in the suprachiasmatic nucleus coordinates peripheral clocks via neurohumoral feedback involving proteins like CLOCK, BMAL1, CRY 1/2, and PER 1-3. In the ICU, these circadian processes often face disruptions from constant lighting, noise, and irregular sleep-wake cycles, impairing sleep quality and worsening stress responses. These disruptions can lead to adverse clinical effects, including higher cardiovascular complication rates. This study examines how ICU stays affect circadian rhythm regulators and their association with cardiovascular outcomes.

RESULTS

Significant differences were identified in melatonin levels and the expression of BMAL1, PER1, RORA, and NR1D1 between ICU stays of ≤7 days and >7 days. The APACHE-II severity scale influenced melatonin and the expression of CLOCK, PER2, CRY2, and RORA. Nonlinear relationships were observed between melatonin, clock genes, heart rate, and blood pressure (systolic and diastolic). In certain groups, molecular and physiological data showed correlations exceeding 90%.

CONCLUSIONS

These findings highlight a robust association between circadian disruption, as measured by melatonin and clock genes, and cardiovascular physiological rhythms in ICU patients.

摘要

背景

由生物钟驱动的昼夜节律有助于生物体使其生理功能与环境变化保持一致,促进体内平衡。视交叉上核中的中央时钟通过涉及CLOCK、BMAL1、CRY 1/2和PER 1-3等蛋白质的神经体液反馈来协调外周时钟。在重症监护病房(ICU),这些昼夜节律过程常常因持续光照、噪音和不规律的睡眠-觉醒周期而受到干扰,损害睡眠质量并加重应激反应。这些干扰可导致不良临床后果,包括更高的心血管并发症发生率。本研究探讨ICU住院如何影响昼夜节律调节因子及其与心血管结局的关联。

结果

在住院时间≤7天和>7天的ICU患者之间,褪黑素水平以及BMAL1、PER1、RORA和NR1D1的表达存在显著差异。急性生理与慢性健康状况评分系统(APACHE-II)严重程度量表影响褪黑素以及CLOCK、PER2、CRY2和RORA的表达。观察到褪黑素、时钟基因、心率和血压(收缩压和舒张压)之间存在非线性关系。在某些组中,分子和生理数据显示相关性超过90%。

结论

这些发现突出了以褪黑素和时钟基因为衡量指标的昼夜节律紊乱与ICU患者心血管生理节律之间的紧密关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4c/11832861/0619abbca7b4/40635_2025_730_Fig1_HTML.jpg

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