基于辐射防护基因集预测的辐射损伤防护化合物活性评价  

Radioprotective Effect of Radioprotectant Predicted by Ra⁃dioprotective Gene Sets

作　　者：贾广彦 刘祯 钱坤 周喆 JIA Guang-Yan;LIU Zhen;QIAN Kun;ZHOU Zhe(Beijing Institute of Radiation Medicine,Beijing 100850;PLA 960 Hospital,Jinan 250031,China)

机构地区：[1]军事医学研究院辐射医学研究所,北京100850 [2]解放军960医院,山东济南250031

出　　处：《生物技术通讯》2020年第6期693-697,共5页Letters in Biotechnology

摘　　要：目的:利用辐射损伤动物模型,评价基于辐射防护基因集预测化合物的防护作用。方法:C57BL/6J小鼠随机分为辐射对照组、氨磷汀(150 mg/kg)组、预测结构组[包括来那度胺(200 mg/kg)组和醛脱氢酶-2激动剂(5 mg/kg)组],各组给药后接受致死剂量8 Gy ^60COγ射线一次性全身照射,观察30 d存活率,挑选辐射损伤防护效果较好的结构。小鼠注射生理盐水、氨磷汀、辐射损伤防护效果较好的药物来那度胺后给予6.5 Gy ^60COγ射线一次性全身照射,另设正常组作为完全对照,各组于照射后第4、7、11、18、21 d尾静脉取血,检测外周血相关指标,第14 d取股骨,HE染色观察骨髓病理学变化。结果:与辐射对照相比,来那度胺可显著提高辐射小鼠生存率;来那度胺组小鼠外周血中淋巴细胞、白细胞、血小板含量均明显提高(P<0.05);来那度胺可增强小鼠的骨髓造血功能,减轻脂肪化。结论:来那度胺具有辐射损伤防护作用,机制涉及促进造血功能恢复等。Objective:To investigate the protective effects of chemicals predicted by radioprotective gene on radi⁃ation-injured mice.Methods:Male C57BL/6J mice were randomized into radiation control(constant volume normal saline)group,amifostine(150 mg/kg)group,predicted chemicals lenalidomide(200 mg/kg)and ALDA-1(5 mg/kg)group.Radiation-injured model was induced by a lethal dose(8 Gy)of total body irradiation(TBI)after the admin⁃istration of chemicals.After irradiation,survival rate of mice within 30 d was determined to select the effective ra⁃dioprotectors.Furthermore,after the administration of saline,radioprotector amifostine,lenalidomide,the mice were exposed to a sub-lethal dose(6.5 Gy)irradiation.Peripheral blood was collected from the tail vein of each group of mice at 4,7,11,18 and 21 days after TBI and peripheral blood cells index were tested.Bone marrow of the experimental mice was observed by HE staining 14 days after TBI.Results:Compared with the radiation control group,lenalidomide treated significantly increased the 30-day survival rate of the irradiated mice.The lympho⁃cytes,white blood cells,platelet content of lenalidomide group were significantly increased(P<0.05).Lenalidomide also promoted the proliferation of cells related to hematopoietic system,enhanced hemopoiesis function of the irradi⁃ated mice.Conclusion:The predicted chemical lenalidomide has protective effect on ^60COγ-rays irradiated mice.The mechanism may be related to improve the hematopoietic function in irradiated mice.

关 键 词：药物重定位 抗辐射药物 来那度胺 

分 类 号：R818[医药卫生—放射医学]