Abstract：
Proton is a major particle of space radiation environment and a prospective radiotherapy beam. However, its risk needs to be fully evaluated for the understanding and to establish the better protective strategy for astronaut and patient. Zebrafish is an ideal model for the toxicity studies on medicines and environmental genetic toxicants. In the current study, embryos of zebrafish at 24 h post-fertilization (hpf) were exposed to proton beam. Some toxic parameters of embryo-larval development were investigated. Microarray combining with qRT-PCR were used to detect the gene expression situation. Generally, fractions of a variety of abnormal phenotypes of embryos and larvae increased in a dose-dependent manner after irradiation. The copy number of mitochondria, the basal respiration rate and the maximum respiration rate of embryos significantly decreased after irradiation. Microarray data demonstrated that MAPK signaling pathway, cell communication, glycolysis and TGF-β signaling pathway were significantly affected in the irradiated group. The expressions of matrix metallopeptidase 9 (mmp9) and TIMP metallopeptidase inhibitor 2b (timp2b) genes, and enzymatic activity of MMP9 were significantly upregulated in irradiated group. Overall, these results suggest that acute radiation of proton severely affects the development of organism and results in aberration occurrence in the early stage of zebrafish development, which may relates to mitochondrial and glycolytic dysfunction.
摘要：
质子是空间辐射环境的主要粒子，是一种前瞻性的放射治疗束。然而,需要对其风险进行充分评估，以了解宇航员和患者，并建立更好的保护策略。斑马鱼是药物和环境遗传毒性研究的理想模型。在目前的研究中,斑马鱼胚胎在24小时受精后（hpf）暴露于质子束。研究了胚胎幼虫发育的一些毒性参数。微阵列结合qRT-PCR检测基因表达情况。一般来说,辐射后，胚胎和幼虫的各种异常表型的分数以剂量依赖性方式增加。线粒体的拷贝数,辐照后胚胎的基础呼吸速率和最大呼吸速率显着降低。微阵列数据表明，MAPK信号通路，细胞通讯，照射组糖酵解和TGF-β信号通路受到显著影响。基质金属肽酶9(mmp9)和TIMP金属肽酶抑制剂2b(timp2b)基因的表达,照射组MMP9酶活性明显上调。总的来说,这些结果表明，质子的急性辐射严重影响生物体的发育，并导致斑马鱼发育早期的畸变发生，这可能与线粒体和糖酵解功能障碍有关。
