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Science: miRNA可预测辐射损伤

miRNA这种小分子自被发现就一直出乎人们的意料,在多个生物学过程中扮演了重要的角色。最新一项研究指出,这种小分子RNA除了在癌症等疾病的诊断和治疗中作用突出,而且也能在生物机体接触辐射24小时内预测辐射造成的长期损伤,其速度比现有的估计辐射吸收剂量的方法要快得多。

这一研究成功公布在5月13日的Science Translational Medicine杂志上。

来自Dana-Farber癌症研究院的研究人员提出了这种新颖的血液检测方法,临产前试验表明这种方法能在24小时内揭示放射性事故受害者的生死,以及他们所受辐射的剂量,这会引发严重的骨骼损伤,还是其它器官的损伤。研究人员表示这种检测能“帮助及时的进行医疗干预,改善患者的整体生存条件。”

来自核电厂、放射性材料、核武器及其他辐射源的高能辐射会导致患者活组织损伤,甚至患上癌症及感染。身体中对辐射毒性最易感的是造血系统,它是由血液和造血器官组成的。接触放射后的损伤需要数周或数月才能表现出来,这会阻碍及时的医疗,而目前用于预测患者体内辐射剂量的方法是检测白细胞的丧失、DNA的损伤或染色体异常,这些测试常常繁琐且耗时。

而这种方法与目前的方法不同,采用的是血液中独特的生物标记物:miRNA,这些分子未来也许能作为诊断性生物标记来指导辐射意外受害者早期治疗。

研究人员让小鼠接触低、高和致死剂量的全身辐射,并在接触辐射24小时内检测血中的miRNA浓度,结果发现在筛选的170个miRNAs中有68种血清miRNAs在辐射发生前后出现了变化,并且能作为“辐射剂量的信号指标”。这些miRNAs能区分致命和非致命放射剂量,并准确地预测总体生存期。

同时研究人员也分析了辐射药物治疗与miRNAs的相关性,他们发现小鼠在接触致命放射剂量前接受抗辐射药物治疗,其RNA表达谱反映了药物的保护作用,并能预测所受的损伤严重程度较低。而对于致命辐射剂量后接受骨髓移植的小鼠,miRNAs也同样具有标识作用。

这些结果表明,miRNA能在辐射暴露后24小时内发生变化,因此能作为早期诊断与治疗的生物标记,应用与辐射治疗中。

参阅文献:
Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury.
Sci Transl Med 13 May 2015:
Vol. 7, Issue 287, p. 287ra69
Sci. Transl. Med. DOI: 10.1126/scitranslmed.aaa6593

Abstract: Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation.
 

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