GANRA纳米药物的辐射防护作用及其对辐射敏感microRNA的影响
发布时间：2018-08-07 11:00
【摘要】：电离辐射广泛存在于太空、核设施及放射医疗过程中,对人类生命安全造成极大的威胁,因此,研制有效的辐射防护药物具有重要意义。GANRA药物是本研究室前期合成的一类新型辐射防护药物,可以有效清除电离辐射产生的自由基,具有良好的辐射防护作用。但是GANRA药物难溶于水,为之后的应用推广造成极大的困难。本研究利用亲水性纳米分子材料包裹GANRA药物制成GANRA纳米药,显著提高了其水溶性。为进一步评估GANRA纳米药物的辐射防护作用,我们以淋巴母细胞(PENG-EBV)作为细胞模型,以细胞增殖率、微核率以及胞内自由基(ROS)含量等为检测指标,测定了GANRA纳米药对淋巴母细胞的毒性作用和辐射防护效果。结果显示:GANRA纳米药物对细胞增殖没有抑制作用。GANRA纳米药预处理可以显著缓解X-射线照射引发的淋巴母细胞增殖速度降低,提高受辐照细胞的活性,降低受辐照细胞的微核形成率,并且对X-射线辐照产生的ROS具有良好的清除作用。前期的实验研究还发现:电离辐射影响循环血中免疫相关的microRNAs(miR-150,miR-574,miR-223和miR-34a)表达。为了进一步确定电离辐射对人淋巴母细胞中microRNAs的影响,我们检测了不同剂量的X-射线辐照及GANRA纳米药物处理对细胞中miR-150,miR-574,miR-223和miR-34a的影响。结果显示:X-射线辐照可以明显改变淋巴母细胞中miR-150,miR-574,miR-223和miR-34a的表达。GANRA纳米药单独处理可以提高淋巴母细胞中miR-150,miR-574,miR-223和miR-34a表达水平,GANRA纳米药预处理可以降低淋巴母细胞中因X-射线或~12C~(6+)辐照诱导的miR-150,mi R-574,mi R-223和miR-34a表达变化。最后,通过转染miR-574类似物,研究了miR-574对电离辐射引起的淋巴母细损伤的影响。发现转染mi R-574类似物,可以缓解淋巴母细胞因X-射线辐射导致细胞活性降低、微核率和细胞内ROS水平的升高。推测GANRA纳米药可能是通过miR-574减少细胞的辐损伤并起到辐射防护作用。以上结果表明GANRA纳米药物可以作为一种有潜力的辐射防护药物。此外,GANRA纳米药物预处理导致的辐射敏感miRNA的差异性表达,可能是GANRA纳米药物发挥辐射防护作用的一种机制。
[Abstract]:The widespread presence of ionizing radiation in space, nuclear facilities and radiotherapeutic processes poses a great threat to the safety of human life. It is of great significance to develop effective radiation protection drugs. GannRA is a kind of new radiation protection drugs synthesized in our laboratory. It can effectively scavenge the free radicals produced by ionizing radiation and has good radiation protection effect. However, GANRA drugs are insoluble in water, causing great difficulties for later application. In this study, GANRA nanopharmaceuticals were prepared by encapsulating GANRA drugs with hydrophilic nanomolecular materials, and their water solubility was improved significantly. In order to further evaluate the radiation protection of GANRA nanopharmaceuticals, we used lymphoblastic cells (PENG-EBV) as cell model, cell proliferation rate, micronucleus rate and intracellular free radical (ROS) content as the detection index. The toxic effect and radiation protective effect of GANRA nanoparticles on lymphoblastic cells were determined. The results showed that the proliferation of lymphoblastocytes induced by X- ray irradiation was significantly reduced and the activity of irradiated cells was increased. The micronucleus formation rate of irradiated cells was decreased, and the ROS produced by X- ray irradiation was removed well. Previous studies have also shown that ionizing radiation affects the expression of immune-related microRNAs (miR-150 miR-574, miR-223 and miR-34a) in circulating blood. In order to determine the effect of ionizing radiation on microRNAs in human lymphoblastic cells, we examined the effects of different doses of X- ray irradiation and GANRA nanopharmaceutical treatment on the miR-150 miR-574 miR-223 and miR-34a in human lymphoblastoid cells. The results showed that the expression of miR-150 miR-574miR-223 and miR-34a in lymphoblastic cells could be obviously changed by the irradiation of w ~ (-) -ray. The pretreatment of miR-150 miR-574 miR-223 and miR-34a in lymphoblastocytes alone could increase the expression level of miR-150 miR-574mmiR-223 and miR-34a. Pretreatment with GANRA nanopharmaceuticals could reduce the expression of miR-150, miR-574miR-223 and miR-34a in lymphoblastocytes. The changes of expression of miR-150Mi R-574mi R-223 and miR-34a induced by X-rays or 12C6 irradiation were observed. Finally, by transfection of miR-574 analogue, the effect of miR-574 on lymphatic mother damage induced by ionizing radiation was studied. It was found that the transfection of mi R-574 analogue could alleviate the decrease of cell activity, the increase of micronucleus rate and the increase of intracellular ROS level in lymphoblastocytes induced by X- ray radiation. It is speculated that GANRA nanopharmaceuticals may reduce radiation damage and protect cells from radiation through miR-574. These results suggest that GANRA nanopharmaceuticals can be used as a potential radiation protection drug. In addition, the differential expression of radiosensitive miRNA induced by GANRA nanopharmaceuticals pretreatment may be a mechanism of radiation protection of GANRA nanopharmaceuticals.
【学位授予单位】：中国科学院大学(中国科学院近代物理研究所)
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R818
[Abstract]:The widespread presence of ionizing radiation in space, nuclear facilities and radiotherapeutic processes poses a great threat to the safety of human life. It is of great significance to develop effective radiation protection drugs. GannRA is a kind of new radiation protection drugs synthesized in our laboratory. It can effectively scavenge the free radicals produced by ionizing radiation and has good radiation protection effect. However, GANRA drugs are insoluble in water, causing great difficulties for later application. In this study, GANRA nanopharmaceuticals were prepared by encapsulating GANRA drugs with hydrophilic nanomolecular materials, and their water solubility was improved significantly. In order to further evaluate the radiation protection of GANRA nanopharmaceuticals, we used lymphoblastic cells (PENG-EBV) as cell model, cell proliferation rate, micronucleus rate and intracellular free radical (ROS) content as the detection index. The toxic effect and radiation protective effect of GANRA nanoparticles on lymphoblastic cells were determined. The results showed that the proliferation of lymphoblastocytes induced by X- ray irradiation was significantly reduced and the activity of irradiated cells was increased. The micronucleus formation rate of irradiated cells was decreased, and the ROS produced by X- ray irradiation was removed well. Previous studies have also shown that ionizing radiation affects the expression of immune-related microRNAs (miR-150 miR-574, miR-223 and miR-34a) in circulating blood. In order to determine the effect of ionizing radiation on microRNAs in human lymphoblastic cells, we examined the effects of different doses of X- ray irradiation and GANRA nanopharmaceutical treatment on the miR-150 miR-574 miR-223 and miR-34a in human lymphoblastoid cells. The results showed that the expression of miR-150 miR-574miR-223 and miR-34a in lymphoblastic cells could be obviously changed by the irradiation of w ~ (-) -ray. The pretreatment of miR-150 miR-574 miR-223 and miR-34a in lymphoblastocytes alone could increase the expression level of miR-150 miR-574mmiR-223 and miR-34a. Pretreatment with GANRA nanopharmaceuticals could reduce the expression of miR-150, miR-574miR-223 and miR-34a in lymphoblastocytes. The changes of expression of miR-150Mi R-574mi R-223 and miR-34a induced by X-rays or 12C6 irradiation were observed. Finally, by transfection of miR-574 analogue, the effect of miR-574 on lymphatic mother damage induced by ionizing radiation was studied. It was found that the transfection of mi R-574 analogue could alleviate the decrease of cell activity, the increase of micronucleus rate and the increase of intracellular ROS level in lymphoblastocytes induced by X- ray radiation. It is speculated that GANRA nanopharmaceuticals may reduce radiation damage and protect cells from radiation through miR-574. These results suggest that GANRA nanopharmaceuticals can be used as a potential radiation protection drug. In addition, the differential expression of radiosensitive miRNA induced by GANRA nanopharmaceuticals pretreatment may be a mechanism of radiation protection of GANRA nanopharmaceuticals.
【学位授予单位】：中国科学院大学(中国科学院近代物理研究所)
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R818
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