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治疗性低温对表面活性蛋白、抗炎和促纤维化介质的影响。

Effect of therapeutic hypothermia on surfactant proteins, anti-inflammatory and pro-fibrotic mediators.

作者信息

Autilio Chiara, Touqui Lhousseine, Foligno Silvia, Arroyo Raquel, Kingma Paul S, Alonso Alejandro A, Perez-Gil Jesus, De Luca Daniele

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research Institut Hospital 12 de Octubre, Complutense University, Madrid, Spain.

Centre de Recherche Saint-Antoine (CRSA)-INSERM U938, Sorbonne Université, Paris, France.

出版信息

J Perinatol. 2025 Apr 2. doi: 10.1038/s41372-025-02285-2.

DOI:10.1038/s41372-025-02285-2
PMID:40175710
Abstract

OBJECTIVES

To study the effect of hypothermia on surfactant proteins, anti-inflammatory and pro-fibrotic mediators DESIGN: Prospective, pragmatic study enrolling asphyxiated neonates without lung injury. Surfactant proteins (SP), Club cell secretory protein (CC-10), tumor growth factor-β1 (TGF-β1), human fibroblast growth factor-2 (hFGF) and anti-inflammatory interleukins (IL) were measured in broncho-alveolar lavage fluids obtained before, during and after hypothermia.

RESULTS

Twelve neonates were studied. SP-A, -B, -C, -D and CC-10 levels were similar before, during and after hypothermia. IL-10, IL-13, IL-14 were inconsistently detected only in five out of twelve patients and not in all timepoints; TGF-β1 was always undetectable. hFGF decreased during hypothermia (pre = 92 [52-193.6], during = 19.4 [0-42.6], post = 31.8 [0-83] ng/mL, p = 0.026) with levels before hypothermia being significantly higher than those obtained during and after the treatment (post hoc p = 0.025).

CONCLUSIONS

In cooled neonates without any lung disorder, hypothermia is associated with lower hFGF but not with any changes in surfactant proteins or anti-inflammatory molecules.

摘要

目的

研究低温对表面活性蛋白、抗炎和促纤维化介质的影响。

设计

一项前瞻性、实用性研究,纳入无肺损伤的窒息新生儿。在低温治疗前、治疗期间和治疗后采集的支气管肺泡灌洗液中检测表面活性蛋白(SP)、克拉拉细胞分泌蛋白(CC-10)、肿瘤生长因子-β1(TGF-β1)、人成纤维细胞生长因子-2(hFGF)和抗炎白细胞介素(IL)。

结果

研究了12例新生儿。低温治疗前、治疗期间和治疗后,SP-A、-B、-C、-D和CC-10水平相似。IL-10、IL-13、IL-14仅在12例患者中的5例中检测结果不一致,且并非在所有时间点均能检测到;TGF-β1始终未检测到。低温治疗期间hFGF水平降低(治疗前=92[52-193.6],治疗期间=19.4[0-42.6],治疗后=31.8[0-83]ng/mL,p=0.026),治疗前水平显著高于治疗期间和治疗后水平(事后检验p=0.025)。

结论

在无任何肺部疾病的低温治疗新生儿中,低温与较低的hFGF相关,但与表面活性蛋白或抗炎分子的任何变化无关。

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本文引用的文献

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Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics.肺疾病中的 club 细胞分泌蛋白:新出现的概念和潜在的治疗方法。
Annu Rev Med. 2023 Jan 27;74:427-441. doi: 10.1146/annurev-med-042921-123443. Epub 2022 Nov 30.
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Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome.治疗性低温可减轻急性呼吸窘迫综合征猪模型中损伤的生理、组织学和代谢组学标志物。
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Mild Hypothermia via External Cooling Improves Lung Function and Alleviates Pulmonary Inflammatory Response and Damage in Two-Hit Rabbit Model of Acute Lung Injury.
轻度外部冷却诱导的低体温改善二次打击兔急性肺损伤模型的肺功能并减轻肺炎症反应和损伤。
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Successful use of mild therapeutic hypothermia as compassionate treatment for severe refractory hypoxemia in COVID-19.成功应用轻度治疗性低体温作为 COVID-19 严重难治性低氧血症的同情治疗。
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Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia.控制性低温治疗期间肺表面活性剂功能增强的分子和生物物理机制。
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SP-D attenuates LPS-induced formation of human neutrophil extracellular traps (NETs), protecting pulmonary surfactant inactivation by NETs.SP-D 可减弱 LPS 诱导的人中性粒细胞胞外诱捕网(NETs)的形成,从而保护肺表面活性剂免受 NETs 的失活。
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