基于造血干细胞保护的黄酮类化合物去氢雌马酚辐射损伤防护作用及其机制研究

Development of radioprotectants is an important medical countermeaure to improve the public against radiation injuries and nuclear attacks. To date, no ideal radioprotectants have been identified due to the insufficient drug research on safety, efficacy and underlying mechanisms.Given the unique radioprotective effects and safety evaluation,flavonoids have been loaded more attention as candidate radioprotective drugs. In our experiments, we demonstrated that one compound of flavonoids,dehydroequol(DHE),had significant radioprotective effects on the 30-day survival rates of mice exposed to high dose TBI.Oral administration of DHE also increased the recovery of bone marrow cells and peripheral blood hematology in lethally irradiated mice.This effect may be associated with the stimulation and preservation of hematopoietic stem and progenitor cells.Besides the significant radioprotective efficacy, the advantages of DHE in the stage of clinical development,good safety and oral administration make this flavonoid be promising as a candidate countermeasure.To pursue this possibility, in this project we will further determine the most effective administration regimen of DHE, demonstrate the radioprotective efficacy on hematopoietic system injuries and elucidate the underling mechanisms based on the potential effects on HSCs/HPCs. We believe our research will provide new tools on development of promising candidate radioprotective agents and new insights in the advancement of radioprotective mechanisms.

辐射防护药物是提高核与辐射医学救护能力的重要措施，但目前因安全性、有效性及作用机制研究的不足使得我们尚未研发出较理想的辐射防护剂。黄酮类化合物因其良好的辐射防护效果及安全性愈来愈受到人们的关注。我们通过前期存活实验、外周血象及造血干细胞分析发现，黄酮类化合物去氢雌马酚（dehydroequol，DHE）可显著提高照射小鼠的存活率，促进造血细胞的恢复，增加HSCs/HPCs的比例，显示出较好的辐射防护作用，效果优于现有药物Genistein。加之DHE已作为临床药物开发，安全性高，口服给药等优势，可作为有希望的辐射防护候选药物加以深入研究。本项目我们拟从DHE最佳给药方案、造血系统防护及基于造血干细胞的机制研究等方面，在动物整体、细胞及分子水平上深入研究DHE的辐射防护作用及作用机制，为确证DHE的辐射防护效果，揭示可能的辐射防护新机制，开发新的化合物提高参考和借鉴。