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晚期糖基化终末产物受体(RAGE)和水通道蛋白5(AQP5)作为溺水诊断新生物标志物的潜在法医学应用。

Potential forensic application of receptor for advanced glycation end products (RAGE) and aquaporin 5 (AQP5) as novel biomarkers for diagnosis of drowning.

作者信息

Lee So-Yeon, Ha Eun-Ju, Cho Hye-Won, Kim Hye-Rim, Lee Dongsup, Eom Yong-Bin

机构信息

Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea.

Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea.

出版信息

J Forensic Leg Med. 2019 Feb;62:56-62. doi: 10.1016/j.jflm.2019.01.007. Epub 2019 Jan 17.

Abstract

Drowning is the most common cause of unnatural death worldwide. There is no single biomarker to diagnose drowning, so the diagnosis of drowning is one of the most difficult tasks in forensic medicine. Especially, distinguishing a victim of drowning from a body disposed of in water following death remains a problem. The objective of this study was to identify specific biomarkers of drowning compared with other causes of death such as hypoxia and postmortem submersion. The present study investigated the intrapulmonary expression of receptor for advanced glycation end products (RAGE), aquaporin-5 (AQP5), surfactant protein-A (SP-A), interleukin 6 (IL-6) and interleukin 1β (IL-1β) as markers of drowning. In animal experiments, all rats (n = 45) were classified into four groups (drowning, postmortem-submersion, hypoxia and control group). The lungs of experimental animals were analyzed as mRNA expression, immunoblot expression and immunohistochemical staining. qRT-PCR demonstrated increased mRNA expression of RAGE and AQP5 in drowning group compared with that in control, hypoxia and postmortem-submersion group, but not other molecules. Western blotting also showed high expression of RAGE and AQP5 in drowning group, immunostaining of RAGE and AQP5 was highly detected in a linear pattern in type I alveolar epithelial cells, compared with control and postmortem-submersion group. These observations indicate a difference of expression in pulmonary molecular pathology compared with other causes, suggesting RAGE and AQP5 may be useful for differentiation between drowning and postmortem-submersion.

摘要

溺水是全球非自然死亡的最常见原因。目前尚无单一生物标志物可用于诊断溺水,因此溺水的诊断是法医学中最困难的任务之一。特别是,区分溺水受害者与死后抛尸入水的尸体仍然是一个难题。本研究的目的是确定与其他死因(如缺氧和死后浸水)相比溺水的特异性生物标志物。本研究调查了晚期糖基化终末产物受体(RAGE)、水通道蛋白-5(AQP5)、表面活性蛋白-A(SP-A)、白细胞介素6(IL-6)和白细胞介素1β(IL-1β)在肺内的表达,作为溺水的标志物。在动物实验中,所有大鼠(n = 45)被分为四组(溺水组、死后浸水组、缺氧组和对照组)。对实验动物的肺组织进行mRNA表达、免疫印迹表达和免疫组织化学染色分析。qRT-PCR结果显示,与对照组、缺氧组和死后浸水组相比,溺水组RAGE和AQP5的mRNA表达增加,但其他分子无此变化。蛋白质免疫印迹法也显示溺水组RAGE和AQP5高表达,与对照组和死后浸水组相比,RAGE和AQP5在I型肺泡上皮细胞中呈线性高表达。这些观察结果表明,与其他死因相比,肺分子病理学存在表达差异,提示RAGE和AQP5可能有助于区分溺水和死后浸水。

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