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创伤性脑损伤与自噬:一项关于人类尸检样本中LC3B、Beclin 1、p62和LAMP2A免疫组化表达的初步研究。

Traumatic brain injury and autophagy: a pilot study about the immunohistochemical expression of LC3B, Beclin 1, p62, and LAMP2A in human autoptic samples.

作者信息

Livieri Tommaso, Alfieri Letizia, Giacomello Emiliana, Alempijević Djordje, Petrovic Tijana, Kolev Yanko Georgiev, Radaelli Davide, Neri Margherita, D'Errico Stefano

机构信息

Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy.

Department of Medical Sciences, Section of Legal Medicine, University of Ferrara, Ferrara, Italy.

出版信息

Front Mol Neurosci. 2025 Apr 28;18:1562954. doi: 10.3389/fnmol.2025.1562954. eCollection 2025.

DOI:10.3389/fnmol.2025.1562954
PMID:40356869
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12066584/
Abstract

INTRODUCTION

Autophagy is a cellular stress response that has been shown in the literature to be active in cerebral cells after a traumatic brain injury (TBI). The aim of this study is to investigate the potential use of four proteins involved in autophagy (LC3B, Beclin 1, p62, and LAMP2A), as a forensic diagnostic marker for TBI.

METHODS

We analyzed histological samples obtained from the frontal lobe of 10 subjects who died within 1 h of a TBI (Group A), 13 who died between 1 h and 32 days post-TBI (Group B), and a control group of 10 subjects who died without head trauma (Group C). Immunohistochemical (IHC) staining using anti-LC3B, anti-Beclin 1, anti-p62 and anti-LAMP2A antibodies was performed.

RESULTS AND DISCUSSION

The results show that LC3B staining was the only one that show a statistically significant difference between groups. In particular, the percentage of neurons displaying an autophagic pattern was calculated from six random acquisitions per subject, and the results were compared across groups using one way ANOVA. Significant differences were observed between Groups A and B, and between Groups B and C, with -values of 0.0055 and 0.0035, respectively. While the difference between Groups A and C was not statistically significant (-value of 0.9845). These findings suggest that LC3B may serve as a useful diagnostic marker for TBI in cases where death is not immediate and open the door for further research.

摘要

引言

自噬是一种细胞应激反应,文献表明其在创伤性脑损伤(TBI)后在脑细胞中具有活性。本研究的目的是调查参与自噬的四种蛋白质(LC3B、Beclin 1、p62和LAMP2A)作为TBI法医诊断标志物的潜在用途。

方法

我们分析了从10名在TBI后1小时内死亡的受试者(A组)、13名在TBI后1小时至32天内死亡的受试者(B组)的额叶获取的组织学样本,以及10名无头部外伤死亡的受试者作为对照组(C组)。使用抗LC3B、抗Beclin 1、抗p62和抗LAMP2A抗体进行免疫组织化学(IHC)染色。

结果与讨论

结果表明,LC3B染色是唯一在各组之间显示出统计学显著差异的染色。具体而言,从每位受试者的六次随机采集计算显示自噬模式的神经元百分比,并使用单因素方差分析在各组之间比较结果。在A组和B组之间以及B组和C组之间观察到显著差异,p值分别为0.0055和0.0035。而A组和C组之间的差异无统计学意义(p值为0.9845)。这些发现表明,LC3B可能作为非即时死亡情况下TBI的有用诊断标志物,并为进一步研究打开了大门。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b98/12066584/40458a1d76c4/fnmol-18-1562954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b98/12066584/b967f1238521/fnmol-18-1562954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b98/12066584/40458a1d76c4/fnmol-18-1562954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b98/12066584/b967f1238521/fnmol-18-1562954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b98/12066584/40458a1d76c4/fnmol-18-1562954-g002.jpg

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本文引用的文献

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Traumatic axonal injury: neuropathological features, postmortem diagnostic methods, and strategies.创伤性轴索损伤:神经病理学特征、死后诊断方法和策略。
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Forensic biomarkers of lethal traumatic brain injury.致死性创伤性脑损伤的法医生物标志物。
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The Emerging Roles of Autophagy in Human Diseases.自噬在人类疾病中的新作用。
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