基于生物信息学分析的辐射致小鼠脑损伤机制

IF 2.5 3区 医学 Q2 BIOLOGY
Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang
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引用次数: 0

摘要

放射治疗是头颈部肿瘤以及原发性或转移性脑肿瘤的重要辅助治疗方法。辐射性脑损伤是头颈部肿瘤患者放疗后最严重的并发症之一,严重影响患者的生活质量。目前,辐射性脑损伤还没有有效的治疗方法,因此研究辐射诱导的分子机制和早期损伤生物标志物的鉴定对于早期诊断和治疗这类损伤至关重要。本研究选取6-8周龄雄性C57小鼠12只,随机分为对照组、15 Gy辐照组和30 Gy辐照组。小鼠暴露在6 MV X射线下。对照组接受与放疗组相同的麻醉过程,但未接受放疗。监测和记录一般健康和体重变化。放疗后4个月,对小鼠进行颅内磁共振成像[t2加权成像(T2WI)]、开放场测试(OFT)、新目标识别(NOR),然后采集脑组织进行免疫荧光、SA-β-gal染色、转录组学和代谢组学分析。与对照组相比,15 Gy和30 Gy辐照的小鼠活动减少,体重减轻。受辐射的小鼠在NOR测试中表现出识别记忆受损和体重下降,但辐射对OFT中的体重或表现没有显著影响。电子显微镜显示辐照后小鼠皮层明显脱髓鞘,MRI t2加权成像显示与对照组相比,辐照小鼠不同程度的脑萎缩和心室增大。免疫荧光染色显示辐照后活化的星形胶质细胞和小胶质细胞明显增加。SA-β-gal染色显示,与未处理的对照组小鼠相比,辐照小鼠的β-gal+细胞数量显著增加。生物信息学分析确定了主要与脂质代谢和神经炎症反应相关的富集通路;相关的代谢物和基因被上调或下调。研究结果表明,放射性脑损伤涉及复杂的生物学过程,脂质代谢紊乱和神经炎症是观察到的主要病理改变。对这些代谢途径和基因的进一步研究有助于我们进一步了解辐射脑损伤的致病机制,并确定潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanisms of Radiation-induced Brain Injury in Mice Based on Bioinformatics Analysis.

Radiation therapy is a crucial adjunct treatment for head and neck tumors, as well as primary or metastatic brain tumors. Radiation-induced brain injury is one of the most severe complications, postirradiation, in patients with head and neck tumors, and significantly impacts their quality of life. Currently, there are no effective treatments for radiation-induced brain injury, making the study of radiation-induced molecular mechanisms and the identification of early damage biomarkers critical for the early diagnosis and treatment of such injuries. In this study, twelve male C57 mice aged 6-8 weeks were randomly divided into a control group, a 15 Gy irradiation group, and a 30 Gy irradiation group. Mice were exposed to 6 MV X rays. The control group underwent the same anesthesia procedure as the irradiated groups but did not receive radiation. General health and weight changes were monitored and recorded. Four months postirradiation, mice were subjected to intracranial magnetic resonance imaging [T2-weighted imaging (T2WI)], open field test (OFT), novel object recognition (NOR), followed by a collection of brain tissues for immunofluorescence, SA-β-gal staining, and transcriptomic and metabolomic analyses. Compared to the control group, the 15 Gy and 30 Gy irradiated mice showed reduced activity and weight loss. The irradiated mice exhibited impaired recognition memory in the NOR test and decreased body weight, but radiation had no significant effect on weight or performance in the OFT. Electron microscopy reveals significant demyelination of mouse cortex after irradiation, and MRI T2-weighted imaging demonstrated varying degrees of brain atrophy and ventricular enlargement in irradiated mice compared to the control group. Immunofluorescence staining showed a significant increase in astrocytes and microglia activated after irradiation. SA-β-gal staining revealed significant increases in the numbers of β-gal+ cells in irradiated mice compared to those in untreated control mice. Bioinformatics analysis identified enriched pathways primarily related to lipid metabolism and neuroinflammatory responses; associated metabolites and genes were variously upregulated or downregulated. The findings suggest that radiation-induced brain injury involves complex biological processes, with lipid metabolism disorders and neuroinflammation being the predominant pathological changes observed. Further studies on these metabolic pathways and genes could enhance our understanding of the pathogenic mechanisms underlying radiation-induced brain injury and identify potential therapeutic targets.

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来源期刊
Radiation research
Radiation research 医学-核医学
CiteScore
5.10
自引率
8.80%
发文量
179
审稿时长
1 months
期刊介绍: Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with chemical agents contributing to the understanding of radiation effects.
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