白介素⁃6基因敲除对辐射诱导小鼠造血损伤的影响及相关机制研究  

Effect of Interleukin⁃6 Gene Deletion on Radiation⁃Induced Mouse Hematopoietic Injury and Relative Mechanism

作　　者：戴洋洋 邢爽 栾皓 杨锦坤 乔子肢 张雪文 熊国林 申星 余祖胤 DAI Yang-Yang;XING Shuang;LUAN Hao;YANG Jin-Kun;QIAO Zi-Zhi;ZHANG Xue-Wen;XIONG Guo-Lin;SHEN Xing;YU Zu-Yin(School of Life Science,Anhui Medical University,Hefei 230032,Anhui Province,China;Department of Experimental Hematology and Biochemistry,Beijing Key Laboratory for Radiobiology,Beijing Institute of Radiation Medicine,Beijing 100850,China)

机构地区：[1]安徽医科大学生命科学学院,安徽合肥230032 [2]军事医学研究院辐射医学研究所,北京100850

出　　处：《中国实验血液学杂志》2022年第4期1255-1261,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金面上项目(81773366,81573088,81202147);军队后勤科研计划项目(AWS21J010)。

摘　　要：目的:研究白介素⁃6(IL⁃6)基因敲除对辐射诱导小鼠造血损伤的影响及其相关机制。方法:观察比较^(60)Coγ射线照射前后IL⁃6基因敲除(IL⁃6^(-/-))和野生型(IL⁃6^(+/+))小鼠的外周血象、骨髓中造血干/祖细胞含量、血清IL⁃6和G⁃CSF表达水平,分析经8.0 Gyγ射线照射后IL⁃6^(+/+)和IL⁃6^(-/-)小鼠30 d存活率。结果:IL⁃6^(+/+)小鼠血清中IL⁃6水平[(98.95±3.85)pg/ml]明显高于IL⁃6^(-/-)小鼠[(18.36±5.61)pg/ml](P<0.001)。照射前成年IL⁃6^(-/-)与IL⁃6^(+/+)小鼠外周血象、血清G⁃CSF水平均无明显统计学差异(P>0.05)。8.0 Gyγ射线照射后6 h,IL⁃6^(-/-)小鼠外周血白细胞、中性粒细胞、淋巴细胞、单核细胞、血小板数和血清G⁃CSF水平较IL⁃6^(+/+)小鼠显著下降(P<0.001);8.0 Gyγ射线照射后30 d,IL⁃6^(+/+)和IL⁃6^(-/-)小鼠存活率分别为62.5%和12.5%,死亡鼠平均存活时间分别为16.0±1.0和10.6±5.3 d。6.5 Gyγ射线照射后14 d,IL⁃6^(+/+)和IL⁃6^(-/-)小鼠骨髓有核细胞计数分别为每根股骨(10.0±1.2)×10^(6)和(8.3±2.2)×10^(6)(P>0.05);与IL⁃6^(+/+)小鼠比较,IL⁃6^(-/-)小鼠骨髓中Lin-Sca⁃1-c⁃kit+(LK)比例无明显变化(P>0.05),但Lin-Sca⁃1+c⁃kit+(LSK)比例显著下降(P<0.05)。结论:IL⁃6对小鼠造血辐射损伤具有明显的调控作用,IL⁃6基因缺失抑制辐射诱导的内源性G⁃CSF水平升高,加重电离辐射引起的小鼠造血干细胞损伤和外周血成熟血细胞的减少,导致致死剂量照射小鼠存活时间缩短、存活率明显下降。Objective:To study the effect of interleukin⁃6(IL⁃6)gene deletion on radiation⁃induced hematopoietic injury in mice and relative mechanism.Methods:Before and after whole body 60 Coγ⁃ray irradiation,it was analyzed and compared that the difference of peripheral hemogram,bone marrow hematopoietic stem and progenitor cells conts in IL⁃6 gene knockout(IL⁃6^(-/-))and wild⁃type(IL⁃6^(+/+))mice and serum IL⁃6 and G⁃CSF expression levels in above⁃mentioned mouse were detected.Moreover,30 days survival rate of IL⁃6^(-/-)and IL⁃6^(+/+)mice after 8.0 Gyγ⁃ray irradiation were analyzed.Results:IL⁃6 levels in serum of IL⁃6^(+/+)and IL⁃6^(-/-)mice were respectively(98.95±3.85)pg/ml and(18.36±5.61)pg/ml,which showed a significant statistical differences(P<0.001).There were no significant differences of peripheral blood cell counts and G⁃CSF level in serum between IL⁃6+/+and IL⁃6^(-/-)mice before irradiation(P>0.05).However,the number of leukocytes,neutrophils,lymphocytes,monocytes,platelets in peripheral blood and G⁃CSF level in serum of IL⁃6^(-/-)mice were significantly decreased at 6 h after 8.0 Gyγ⁃ray irradiation compared with that of IL⁃6+/+mice.On days 30 after 8.0 Gyγ⁃ray irradiation,the survival rate of IL⁃6+/+and IL⁃6^(-/-)mice was 62.5%and 12.5%,and the mean survival time of dead mice was 16.0±1.0 and 10.6±5.3 days,respectively.On days 14 after 6.5 Gyγ⁃ray irradiation,bone marrow nucleated cells in IL⁃6+/+and IL⁃6^(-/-)mice were respectively(10.0±1.2)×10^(6)and(8.3±2.2)×10^(6)per femur.Compared with IL⁃6+/+mice,the proportion of Lin-Sca⁃1-c⁃kit+(LK)in bone marrow of IL⁃6^(-/-)mice had no significant change(P>0.05),but the proportion of Lin-Sca⁃1+c⁃kit+(LSK)was significantly decreased(P<0.05).Conclusion:IL⁃6 plays an obvious role in regulating hematopoietic radiation injury,and IL⁃6 deficiency can inhibit the radiation⁃induced increase of endogenous G⁃CSF level in serum,aggravates the damage of mouse hematopoietic stem cells(HSC

关 键 词：白介素⁃6 电离辐射 急性放射病 骨髓抑制 造血损伤 

分 类 号：R818[医药卫生—放射医学] R329[医药卫生—临床医学]