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左旋α-甘油磷酸胆碱作为斑马鱼胚胎模型中的一种潜在辐射防护剂

l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model.

作者信息

Szabó Emília Rita, Plangár Imola, Tőkés Tünde, Mán Imola, Polanek Róbert, Kovács Róbert, Fekete Gábor, Szabó Zoltán, Csenki Zsolt, Baska Ferenc, Hideghéty Katalin

机构信息

1 Attosecond Light Pulse Source, ELI-HU Nonprofit Ltd., Szeged, Hungary .

2 MTA-SE NAP B Cognitive Translational Behavioural Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest, Hungary .

出版信息

Zebrafish. 2016 Dec;13(6):481-488. doi: 10.1089/zeb.2016.1269. Epub 2016 Aug 3.

Abstract

This work establishes the zebrafish embryo model for ionizing radiation (IR) modifier research and also evaluates the protective effect of l-alpha glycerylphosphorylcholine (GPC). Embryos were exposed to a single-fraction whole-body gamma irradiation (5, 10, 15, and 20 Gy) at different postfertilization time points and were serially assessed for viability and macro- and micromorphologic abnormalities. After toxicity evaluation, 194 μM of GPC was added for certain groups with 3-h incubation before the radiation. Nuclear factor kappa B (NF-κB) and interleukin-1β (IL-1β) expression changes were measured using quantitative real-time polymerase chain reaction. A higher sensitivity could be observed at earlier stages of the embryogenesis. The lethal dose (LD) for 6 hours postfertilization (hpf) embryos was 15 Gy and for 24 hpf was 20 Gy on day 7, respectively. GPC administration resulted in a significant improvement in both the distortion rate and survival of the 24 hpf embryos. Qualitative evaluation of the histological changes confirmed the protective effect of GPC. IL-1β and NF-κB overexpression due to 10 Gy irradiation was also reduced by GPC. GPC exhibited promising radioprotective effects in our zebrafish embryo model, decreasing the irradiation-induced morphological damage and lethality with significant reduction of IR-caused pro-inflammatory activation.

摘要

本研究建立了用于电离辐射(IR)修饰剂研究的斑马鱼胚胎模型,并评估了l-α甘油磷酸胆碱(GPC)的保护作用。在不同的受精后时间点,将胚胎暴露于单次全身γ辐射(5、10、15和20 Gy),并对其活力以及宏观和微观形态异常进行连续评估。在毒性评估后,对某些组在辐射前3小时加入194μM的GPC进行孵育。使用定量实时聚合酶链反应测量核因子κB(NF-κB)和白细胞介素-1β(IL-1β)的表达变化。在胚胎发育的早期阶段可以观察到更高的敏感性。受精后6小时(hpf)胚胎的致死剂量(LD)在第7天分别为15 Gy,受精后24 hpf胚胎的致死剂量为20 Gy。给予GPC可显著改善24 hpf胚胎的畸变率和存活率。组织学变化的定性评估证实了GPC的保护作用。GPC还降低了10 Gy辐射引起的IL-1β和NF-κB过表达。在我们的斑马鱼胚胎模型中,GPC表现出有前景的辐射防护作用,减少了辐射诱导的形态损伤和致死率,并显著降低了IR引起的促炎激活。

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