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先天性心脏缺陷新生儿心肌中白细胞介素-6和缺氧诱导因子-1α的mRNA表达

Myocardial mRNA expression of interleukin-6 and hypoxia inducible factor-1α in neonates with congenital cardiac defects.

作者信息

Farhat Nesrine, Vazquez-Jimenez Jaime, Heying Ruth, Seghaye Marie-Christine

机构信息

Department of Paediatric Cardiology, University Hospital, Liège, Belgium.

Department of Paediatric Cardiac Surgery, University Hospital, Aachen, Germany.

出版信息

Mol Cell Pediatr. 2024 Dec 21;11(1):14. doi: 10.1186/s40348-024-00187-5.

DOI:10.1186/s40348-024-00187-5
PMID:39708201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11663211/
Abstract

BACKGROUND

In neonates with congenital heart disease (CHD), myocardial remodelling involves activation of inflammatory pathways. The role of hypoxemia related pathways is however unknown. This study was therefore designed to investigate myocardial mRNA expression of interleukin (IL)-6 and hypoxia-inducible factor (HIF)-1α in neonates with CHD and analyse its influence on post-operative outcome.

RESULTS

14 neonates with CHD scheduled for open cardiac surgery were studied. In group 1 (n = 5), pre-operative transcutaneous arterial oxygen saturation (SaO) was ≤ 85% and in group 2 (n = 9) > 85%. Expression of IL-6- and HIF-1α-mRNA was studied on right atrial biopsy by RT-PCR and corelated to post-operative (po) outcome. Group 1 patients showed higher mean arterial blood pressure (MAP) and lower glycaemia 4 h po (p = 0.047 and p = 0.021, respectively). In the whole cohort, SaO correlated negatively with MAP (Pearson R: -0.662, p = 0.010). mRNA coding for IL-6 and HIF-1α was detected in the myocardium of all neonates independently of age, gender, or type of CHD. IL6-mRNA expression was not influenced by pre-operative hypoxemia but was associated with higher lactate levels in early po period (Pearson R: 0,611, p = 0,020). HIF-1α-mRNA expression correlated negatively with pre-operative SaO (Pearson R: -0.551, p = 0.04) and with aspartate aminotransferase levels 4 h po (Pearson R: 0.625, p = 0.017).

CONCLUSION

Our study shows that besides inflammatory pathways, hypoxemia related pathways are activated in the myocardium of neonates with CHD. Myocardial expression of both IL-6-mRNA and HIF-1α-mRNA relates to biological markers of a worse po outcome.

摘要

背景

在患有先天性心脏病(CHD)的新生儿中,心肌重塑涉及炎症途径的激活。然而,低氧血症相关途径的作用尚不清楚。因此,本研究旨在调查患有CHD的新生儿心肌中白细胞介素(IL)-6和缺氧诱导因子(HIF)-1α的mRNA表达,并分析其对术后结局的影响。

结果

对14例计划进行心脏直视手术的患有CHD的新生儿进行了研究。在第1组(n = 5)中,术前经皮动脉血氧饱和度(SaO)≤85%,在第2组(n = 9)中>85%。通过逆转录聚合酶链反应(RT-PCR)研究右心房活检中IL-6和HIF-1α-mRNA的表达,并与术后(po)结局相关联。第1组患者术后4小时平均动脉血压(MAP)较高,血糖较低(分别为p = 0.047和p = 0.021)。在整个队列中,SaO与MAP呈负相关(Pearson相关系数R:-0.662,p = 0.010)。在所有新生儿的心肌中均检测到编码IL-6和HIF-1α的mRNA,与年龄、性别或CHD类型无关。IL6-mRNA表达不受术前低氧血症影响,但与术后早期较高的乳酸水平相关(Pearson相关系数R:0.611,p = 0.020)。HIF-1α-mRNA表达与术前SaO呈负相关(Pearson相关系数R:-0.551,p = 0.04),与术后4小时天冬氨酸转氨酶水平呈正相关(Pearson相关系数R:0.625,p = 0.017)。

结论

我们的研究表明,除了炎症途径外,患有CHD的新生儿心肌中低氧血症相关途径也被激活。IL-6-mRNA和HIF-1α-mRNA的心肌表达均与较差的术后结局的生物学标志物相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/5d797c99abf8/40348_2024_187_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/1674192faa09/40348_2024_187_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/329e50289aac/40348_2024_187_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/4eeeb4953c45/40348_2024_187_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/5d797c99abf8/40348_2024_187_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/1674192faa09/40348_2024_187_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/329e50289aac/40348_2024_187_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/4eeeb4953c45/40348_2024_187_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/11663211/5d797c99abf8/40348_2024_187_Fig4_HTML.jpg

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Interleukin-6 and Hypoxia Synergistically Promote EMT-Mediated Invasion in Epithelial Ovarian Cancer via the IL-6/STAT3/HIF-1 Feedback Loop.白细胞介素-6 和缺氧通过 IL-6/STAT3/HIF-1 反馈环协同促进上皮性卵巢癌细胞中的 EMT 介导的侵袭。
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