芳香烃受体抑制剂SR1对小鼠造血系统辐射损伤的防护作用  

Effect of aryl hydrocarbon receptor antagonist SR1 on radiation-induced hematopoietic system injury in mice

作　　者：周晓靓[1] 李德冠[1] 徐文清[1] 王浩[1,2] Zhou Xiaoliang;Li Deguan;Xu Wenqing;Wang Hao(Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Sciences,Tianjin 300192,China;Academy of Medical Engineering and Translational Medicine,Tianjin University,Tianjin 300072,China)

机构地区：[1]中国医学科学院放射医学研究所,天津市放射医学与分子核医学重点实验室,300192 [2]天津大学医学工程与转化医学研究院,300072

出　　处：《国际放射医学核医学杂志》2021年第6期364-369,共6页International Journal of Radiation Medicine and Nuclear Medicine

基　　金：国家自然科学基金(81502759、81972975);天津市科技支撑重点项目(17YFZCSY00670)。

摘　　要：目的研究芳香烃受体抑制剂StemRegenin 1(SR1)对全身照射后小鼠造血系统辐射损伤的防护作用。方法采用随机化区组设计,将15只健康C57BL/6J小鼠分为3组:对照组、4 Gy照射组(简称照射组)和4 Gy照射+SR1组(简称照射给药组),每组5只。照射给药组在照射前5 d至照射后5 d连续灌胃给予SR1(50 mg/kg),4 Gyγ射线全身照射后第9天处死小鼠,取外周血和单侧股骨细胞,使用全自动血液分析仪检测外周血白细胞(WBC)、红细胞(RBC)、骨髓有核细胞(BMNC)等计数;采用粒细胞-巨噬细胞集落形成单位(CFU-GM)实验检测骨髓细胞增殖能力;使用流式细胞仪检测BMNC和造血干细胞(HSC)中的活性氧(ROS)水平、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)水平和外周血中免疫细胞百分比。组间两两比较采用Student t检验。结果与照射组相比,照射给药组小鼠外周血中WBC[(3.060±0.650)×10^(9)个/mL对(4.680±1.134)×10^(9)个/mL,t=2.770,P<0.05]和BMNC[(28.375±6.811)×10^(9)个/mL对(49.125±12.532)×10^(9)个/mL,t=3.231,P<0.05)]数量均明显增加;与对照组相比,照射给药组RBC数量明显减少(t=4.301,P<0.05)。与照射组相比,照射给药组CFU-GM明显升高(3.4±1.7对13.6±6.7),且差异有统计学意义(t=3.323,P<0.05);照射给药组小鼠的BMNC和HSC中ROS水平明显降低(t=3.962、2.530,均P<0.05),同时BMNC和HSC中NOX4水平亦明显降低(t=2.310、2.848,均P<0.05);照射给药组小鼠CD3+T细胞百分比明显升高[(8.512±3.716)%对(16.140±1.969)%,t=4.056,P<0.05],B220+B细胞百分比亦明显升高[(0.608±0.267)%对(7.240±2.828)%,t=4.027,P<0.05]。结论芳香烃受体抑制剂SR1对全身照射造成的小鼠造血系统辐射损伤有一定的保护作用。Objective To investigate the effect of the aryl hydrocarbon receptor(AHR)antagonist StemRegenin 1(SR1)on the hematopoietic system injury of mice exposed to whole-body radiation.Methods Fifteen C57BL/6J mice were randomized block design to three groups(n=5)in a randomized block design as follows:control,4 Gy,4 Gy+SR1.Mice in the 4 Gy+SR1 group were administered SR1(50 mg/kg)by gavage from 5 d before irradiation to 5 d after irradiation.All of the mice were sacrificed on the ninth day after 4 Gyγ-ray whole-body radiation.Peripheral blood and unilateral femoral cell were harvested and tested by an automatic hematology analyzer for white blood cells(WBC),red blood cells(RBC)and bone marrow nucleated cells(BMNC)counting.The number of colony-forming units-granulocyte-macrophage(CFU-GM)was counted to assess the proliferation of bone marrow cells,and a flow cytometer was used to analyze reactive oxygen species(ROS)levels and the nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression of BNMC and hematopoietic stem cells(HSC).The proportion of immunocytes in peripheral blood was also checked.Student's t-test was applied to compare differences between two groups.Results Compared with those of the 4 Gy group,the WBC((3.060±0.650)×10^(9)/mL vs.(4.680±1.134)×10^(9)/mL,t=2.770,P<0.05)and BMNC((28.375±6.811)×10^(9)/mL vs.(49.125±12.532)×10^(9)/mL,t=3.231,P<0.05)counts of the 4 Gy+SR1 group increased significantly.By contrast,RBC counts in the 4 Gy+SR1 group markedly decreased(t=4.301,P<0.05)compared with those in the control group.CFU-GM was higher in the 4 Gy+SR1 group than in the 4 Gy group(3.4±1.7 vs.13.6±6.7,t=3.323,P<0.05).The ROS levels of BMNC and HSC were obviously induced by radiation but could be rescued by SR1 treatment.Compared with that in the 4 Gy group,the ROS level in the 4 Gy+SR1 group significantly decreased in BMNC(t=3.962,P<0.05)and HSC(t=2.530,P<0.05).Changes in NOX4 expression levels were consistent with those of ROS levels after radiation.The NOX4 expression of BMNC and HSC marked

关 键 词：辐射损伤 造血系统 辐射防护剂 芳香烃受体 StemRegenin 1 

分 类 号：R818.74[医药卫生—放射医学]