FOXO3A对全身照射小鼠造血系统辐射损伤的影响  

Effect of FOXO3A on hematopoietic system damage in total-body irradiated mice

作　　者：王玉全 李程程 苏路路 管博文 卢延华 关菲菲 荣利 王小春 孟爱民 樊飞跃 WANG Yuquan;LI Chengcheng;SU Lulu;GUAN Bowen;LU Yanhua;GUAN Feifei;RONG Li;WANG Xiaochun;MENG Aimin;FAN Feiyue(Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences(CAMS),Comparative Medicine Center,Peking Union Medical College(PUMC),NHC Key Laboratory of Human Disease Comparative Medicine;Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,Beijing 100021,China.2.The Beijing Prevention and Treatment Hospital of Occupational Disease for Chemical Industry,Beijing Institute of Occupational Disease Prevention and Treatment,Beijing 100093)

机构地区：[1]中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家卫生健康委员会人类疾病比较医学重点实验室,北京市人类重大疾病实验动物模型工程技术研究中心,北京100021 [2]北京市化工职业病防治院,北京市职业病防治研究院,北京100093

出　　处：《中国比较医学杂志》2019年第9期10-16,共7页Chinese Journal of Comparative Medicine

基　　金：协和青年基金(2017310015);国家自然科学基金青年基金(81703170)

摘　　要：目的利用FOXO3A基因敲除小鼠探讨FOXO3A在造血系统电离辐射(ionizing radiation,IR)损伤中的影响。方法FOXO3A^-/-小鼠和WT小鼠(FVB/N)分为野生型小鼠对照组(WT组),FOXO3A^-/-小鼠对照组(FOXO3A^-/-组),野生型小鼠照射组(WT+IR),FOXO3A^-/-小鼠照射组(FOXO3A^-/-+IR)四组,分别接受假照射和4 Gy X射线全身照射(total body irradiation,TBI),剂量率为0.9 Gy/min。接受TBI后14 d检测FOXO3A^-/-小鼠和WT小鼠脏器指数、外周血和骨髓细胞计数,骨髓细胞分型,造血祖细胞(HPCs)粒细胞巨噬细胞集落形成单位(colony forming unit-granulocyte and macrophage,CFU-GM)形成能力,观察FOXO3A基因敲除对造血系统辐射损伤的影响。结果生理情况下,FOXO3A^-/-小鼠骨髓有核细胞计数下降,HPCs比例升高(P<0.05);小鼠接受4 Gy X射线TBI后14 d,FOXO3A基因敲除会加重电离辐射诱导的HPCs和造血干细胞(HSCs)比例下降,但也会抑制辐射诱导的骨髓有核细胞数下降和造血祖细胞CFU-GM形成能力减退。结论FOXO3A基因敲除破坏造血系统稳态维持,加重TBI小鼠HPCs和HSCs的辐射损伤,对造血细胞辐射敏感性产生一定的影响。FOXO3A在造血系统电离辐射损伤中的调节作用以及能否作为防治损伤的靶点还有待进一步研究。Objective To explore the effect of FOXO3A on hematopoietic system damage induced by irradiation exposure in FOXO3A-knockout mice.Methods FOXO3A^-/-and WT mice were divided into four groups:wild-type control(WT),FOXO3A^-/-control(FOXO3A^-/-),wild-type irradiation(WT+IR),and FOXO3A^-/-irradiation(FOXO3A^-/-+IR).Mice received 4 Gy X-ray total body irradiation(TBI)at a dose rate of 0.9 Gy/min.Fourteen days later,peripheral blood measurements,bone marrow cell counts,organ index,bone marrow cell phenotyping,and CFU-GM of hematopoietic progenitor cells were quantified.Results Under physiological conditions,bone marrow nucleated cell counts were decreased and proportions of hematopoietic progenitor cells(HPCs)were increased in FOXO3A^-/-mice(P<0.05).These results indicate an increased decline in the proportion of HPCs/hematopoietic stem cells(HSCs),and reduced number of bone-marrow nucleated cells and colony forming unit-granulocyte and macrophage(CFU-GM)(P<0.001)in FOXO3A^-/-mice 14 days after 4 Gy X-ray TBI.Conclusions FOXO3A gene knockout damaged the homeostatic maintenance of the hematopoietic system,and aggravated HPC and HSC injury in TBI mice.The role of FOXO3A in regulation of hematopoietic system damage induced by radiation exposure and clinical translation remain to be further studied.

关 键 词：电离辐射 FOXO3A 造血干细胞 造血祖细胞 活性氧 DNA损伤应答 小鼠 

分 类 号：R-33[医药卫生]