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蛋白质组学分析确定实验性新生儿炎症致敏性缺氧缺血后与治疗成功相关的蛋白质。

Proteomic analysis identifying proteins relevant for treatment success following experimental neonatal inflammation-sensitized hypoxia-ischemia.

作者信息

Burkard Hannah, Osredkar Damjan, Maes Elke, Bernis Maria E, Bremer Anna-Sophie, Zweyer Margit, Dowling Paul, Ohlendieck Kay, Thoresen Marianne, Sabir Hemmen

机构信息

Department of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, 53127, Bonn, Germany.

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 53127, Bonn, Germany.

出版信息

Pediatr Res. 2025 May 13. doi: 10.1038/s41390-025-04097-8.

Abstract

BACKGROUND

Understanding the mechanisms of injury following neonatal hypoxic-ischemic encephalopathy (HIE) is a major goal in neonatal research. HIE can have severe effects on cognitive and motor development in newborns, including an increased risk of death. As the incidence is 10-20 times higher in low- and middle-income countries compared to developed countries, the interest in a therapy exists worldwide. Therapeutic hypothermia (HT) is the only effective treatment after HIE. However, TH is not universally effective, particularly in cases of inflammation-sensitized hypoxia-ischemia (HI); it provides limited benefit.

METHODS

To identify proteins that may contribute to the reduced efficacy of HT in the case of pre-HI inflammation sensitization, the proteomic profiles of animals subjected to HI and HT combined with lipopolysaccharide (LPS) were analyzed via liquid chromatography mass spectrometry (LC-MS/MS).

RESULTS

We identified proteins that potentially support the efficacy of HT and those that prevent the success of the therapy in the neonatal rat model of inflammation-sensitized HI.

CONCLUSION

This study represents a step forward in identifying proteins related to the efficacy of HT following inflammation-sensitized HI.

IMPACT

Therapeutic hypothermia is the only available treatment for neonatal hypoxic-ischemic encephalopathy, but not effective in models of inflammation-sensitized hypoxic-ischemic brain injury. Using liquid chromatography mass spectrometry, we identified proteins possibly having an effect on the treatment success of therapeutic hypothermia following experimental inflammation-sensitized hypoxic-ischemic brain injury. This proteomic analysis reveals proteins as potential markers that could prevent or support the efficacy of therapeutic hypothermia in experimental neonatal inflammation-sensitized hypoxic-ischemic encephalopathy.

摘要

背景

了解新生儿缺氧缺血性脑病(HIE)后的损伤机制是新生儿研究的主要目标。HIE可对新生儿的认知和运动发育产生严重影响,包括死亡风险增加。由于低收入和中等收入国家的发病率比发达国家高10 - 20倍,因此全球都对一种治疗方法感兴趣。治疗性低温(HT)是HIE后的唯一有效治疗方法。然而,HT并非普遍有效,特别是在炎症致敏的缺氧缺血(HI)病例中;其益处有限。

方法

为了确定在HI前炎症致敏情况下可能导致HT疗效降低的蛋白质,通过液相色谱质谱联用(LC-MS/MS)分析了接受HI和HT联合脂多糖(LPS)处理的动物的蛋白质组学图谱。

结果

我们在炎症致敏的HI新生大鼠模型中鉴定出了可能支持HT疗效的蛋白质以及那些阻碍治疗成功的蛋白质。

结论

本研究在鉴定与炎症致敏HI后HT疗效相关的蛋白质方面向前迈进了一步。

影响

治疗性低温是新生儿缺氧缺血性脑病的唯一可用治疗方法,但在炎症致敏的缺氧缺血性脑损伤模型中无效。通过液相色谱质谱联用,我们鉴定出了可能对实验性炎症致敏的缺氧缺血性脑损伤后治疗性低温的治疗成功有影响的蛋白质。这种蛋白质组学分析揭示了蛋白质作为潜在标志物,可预防或支持治疗性低温在实验性新生儿炎症致敏的缺氧缺血性脑病中的疗效。

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