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使用蛋白质组学研究蛛网膜下腔出血后人脑微透析液中转甲状腺素水平的变化;一项描述性初步研究。

Altered levels of transthyretin in human cerebral microdialysate after subarachnoid haemorrhage using proteomics; a descriptive pilot study.

作者信息

Ginstman Fredrik, Ghafouri Bijar, Zsigmond Peter

机构信息

Department of Neurosurgery in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Pain and Rehabilitation Center and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

出版信息

Proteome Sci. 2023 Jul 7;21(1):10. doi: 10.1186/s12953-023-00210-z.

Abstract

BACKGROUND

Subarachnoid haemorrhage (SAH) is one of the most severe forms of stroke in which delayed cerebral ischemia is one of the major complications. Neurointensive care aims at preventing and treating such complications and identification of biomarkers of early signs of ischemia might therefore be helpful.

METHODS

We aimed at describing proteome profile in cerebral microdialysate in four patients with aneurysmal SAH using two dimensional gel electrophoresis in combination with mass spectrometry in search for new biomarkers for delayed cerebral ischemia and to investigate if there were temporal fluctuations in those biomarkers over time after aneurysmal bleed.

RESULTS

The results showed transthyretin in nine different proteoforms (1001, 1102, 2101, 3101, 4101, 4102, 5001, 5101, 6101) in cerebral microdialysate samples from four patients having sustained SAH. Several proteoforms show highly differing levels and pooled analysis of all samples showed varying optical density related to time from aneurysmal bleed, indicating a temporal evolution.

CONCLUSIONS

Transthyretin proteoforms have not earlier been shown in cerebral microdialysate after SAH and we describe differing levels based on proteoform as well as time from subarachnoid bleed. Transthyretin is well known to be synthetized in choroid plexus, whilst intraparenchymal synthesis remains controversial. The results need to be confirmed in larger studies in order to further describe transthyretin.

摘要

背景

蛛网膜下腔出血(SAH)是最严重的中风形式之一,其中迟发性脑缺血是主要并发症之一。神经重症监护旨在预防和治疗此类并发症,因此识别缺血早期迹象的生物标志物可能会有所帮助。

方法

我们旨在通过二维凝胶电泳结合质谱法描述4例动脉瘤性SAH患者脑微透析液中的蛋白质组图谱,以寻找迟发性脑缺血的新生物标志物,并研究这些生物标志物在动脉瘤出血后是否随时间发生波动。

结果

结果显示,在4例持续性SAH患者的脑微透析液样本中,转甲状腺素蛋白有9种不同的蛋白质变体(1001、1102、2101、3101、4101、4102、5001、5101、6101)。几种蛋白质变体显示出高度不同的水平,对所有样本的汇总分析显示,与动脉瘤出血后的时间相关的光密度有所变化,表明存在时间演变。

结论

转甲状腺素蛋白变体在SAH后的脑微透析液中此前尚未见报道,我们描述了基于蛋白质变体以及蛛网膜下腔出血后的时间的不同水平。众所周知,转甲状腺素蛋白在脉络丛中合成,而脑实质内合成仍存在争议。这些结果需要在更大规模的研究中得到证实,以便进一步描述转甲状腺素蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e63/10326944/e9654a00b99d/12953_2023_210_Fig1_HTML.jpg

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