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根据美国食品和药品监督管理局(food and drug administration,FDA)的定义,生物标志物是一种可以被检测到的生化指标,可以反映特定的生理学、病理学或治疗过程,评估不同类型的生物学特性或参数[1]。因此,生物标志物对鉴定疾病表型和开发药物至关重要。生物标志物主要包括基因序列、微小RNA(microRNAs,miRNAs)、长链非编码RNA(long non-coding RNAs,lncRNAs)、代谢物、微生物群、细胞因子和趋化因子等。目前,美国FDA已批准了约150种药物作用于机体后产生的生物标志物[1],然而都与辐射不相关。多个潜在的生物标志物正在确认中,其中一些具有抗辐射应用价值。
抗辐射药物研发已有70年的历史,虽然研究者研发了一些效果较好的药物,但可以应用于临床、效果好且不良反应小的抗辐射药物很少。例如氨磷汀,由于会使患者产生恶心和低血压等不良反应,使得临床应用受限。充分研究辐射损伤的作用机制,对于研发抗辐射药物至关重要,而辐射损伤生物标志物的研究是其中重要的一环。美国FDA明确规定,如果一种生物标志物审查合格,就可以在多个相关的药物中使用,从而加快药物的研发进程[1-2]。
除了与抗辐射药物相关的生物标志物之外,用于评估辐射吸收剂量的生物标志物也很重要。因为在发生大规模的核事故时,需要快速评估大量伤员的个人吸收剂量,并据此制定辐射救治方案。近年来,有研究者尝试用血液学、生化和细胞遗传学参数来估算辐射吸收剂量,如C反应蛋白、淀粉酶和细胞因子,然而这些标志物个体间差异大,并且会随炎症和感染等因素波动[3]。目前,淋巴细胞耗竭分析和双着丝粒染色体分析是用于评估辐射吸收剂量的“金标准”,但是淋巴细胞耗竭分析耗费时间较长,而双着丝粒染色体分析技术含量高,劳动强度大,需要专业人员操作[4]。另外,磷酸化组蛋白H2AX(phosphorylated histone H2AX,γ-H2AX)是检测DNA双链断裂的最佳生物标志物,然而最佳检测时间是照射后0~2 h,随后γ-H2AX表达水平急剧下降,因此检测窗口很窄。综上,新型生物标志物应该对辐射敏感、稳定性好,并且能以非侵入性或微创性的方式进行快速和重复检测。随着代谢组学、免疫组学和基因组学应用于辐射剂量学领域,基因转录标志物(miRNAs、lncRNAs等)、辐射代谢物和新的测量技术等丰富了辐射生物标志物的范围,我们对近年来辐射相关新型生物标志物的最新研究进展予以综述。
辐射损伤相关生物标志物的研究进展
Research progress of biomarkers related to radiation injury
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摘要: 核与辐射事故发生时,快速评估人体吸收的辐射剂量对于伤员的分类和救治极为重要。为制定有效的辐射损伤救治方案和研发抗辐射新药,辐射损伤相关生物标志物的研究引起了研究者的浓厚兴趣。通过辐射损伤相关生物标志物的变化评估辐射吸收剂量或抗辐射药物的有效性成为研究的热点。笔者围绕近年来用于评估辐射吸收剂量和抗辐射药物有效性的生物标志物展开综述。Abstract: The rapid assessment of the radiation dose absorbed by the human body during nuclear and radiation accidents is extremely important for the classification and treatment of the wounded. In order to formulate effective radiation injury treatment strategies and develop new anti-radiation drugs, the research on biomarkers related to radiation injury has aroused strong interest of researchers. Evaluating the radiation absorbed dose or the effectiveness of anti-radiation drugs through changes in radiation damage-related biomarkers has become a research hotspot. Therefore, this paper reviews the biomarkers used in recent years to evaluate the radiation absorbed dose and the effectiveness of anti-radiation drugs.
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Key words:
- Radiation injuries /
- Radiation-protective agents /
- Radiation dosage /
- Biomarkers
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