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西格列汀对小鼠造血系统辐射损伤的治疗作用
引用本文:张远洋,王梅芳,董银萍,吴静,王欣悦,李文璇,李德冠.西格列汀对小鼠造血系统辐射损伤的治疗作用[J].国际放射医学核医学杂志,2021,45(8):515-520.
作者姓名:张远洋  王梅芳  董银萍  吴静  王欣悦  李文璇  李德冠
作者单位:中国医学科学院北京协和医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
摘    要: 目的 探讨西格列汀对7 Gy γ射线照射后小鼠造血系统损伤的治疗作用。 方法 将15只C57BL/6小鼠按照区组随机法分为对照组、照射组、西格列汀+照射组,每组5只。照射组和西格列汀+照射组小鼠接受7 Gy 137Cs γ射线一次性全身照射,后者于照射后2 h开始灌胃西格列汀,给药剂量为10 mg/kg,连续给药7 d;对照组和照射组给予等量生理盐水。照射后第30天取外周血进行血象测定,颈椎脱位处死小鼠后取骨髓细胞测定有核细胞数、造血干细胞(HSC)和造血祖细胞(HPC)数量及其活性氧水平、粒细胞-巨噬细胞集落形成单位(CFU-GM)。2组间的比较采用独立样本t检验。 结果 与对照组比较,照射组小鼠的骨髓有核细胞、白细胞、红细胞、血小板计数和血红蛋白、红细胞比容水平均明显减少、下降(t=3.476~12.200,均P<0.05);HSC和HPC的数量及百分比均明显减少、降低(t=3.174~5.287,均P<0.05);HSC中活性氧水平明显升高(1980.6±309.3对3994.5±1119.0,t=3.904,P<0.05),骨髓细胞CFU-GM显著减少(66.2±5.3对30.8±3.9,t=13.240,P<0.05)。与照射组相比,西格列汀+照射组小鼠骨髓有核细胞(8.0±1.0)×106个对(11.0±0.4)×106个,t=4.593,P<0.05]、白细胞数量(3.0±0.2)×109个/L对(3.9±0.3)×109个/L,t=7.020,P<0.05]均增多;HPC数量(33 724.4±10 594.9)个对(101 637.6±17 240.5)个,t=5.951,P<0.05]及百分比(5.6±1.0)%对(11.5±3.0)%,t=4.163,P<0.05]均上升,HSC中活性氧水平降低(3994.5±1119.0对2415.7±122.9,t=2.375,P<0.05),骨髓细胞CFU-GM增加(30.8±3.9对38.2±4.4,t=2.964,P<0.05)。 结论 西格列汀对7 Gy γ射线照射后小鼠造血系统损伤有一定的治疗作用。

关 键 词:辐射损伤  西格列汀  造血系统  外周血  骨髓细胞  活性氧
收稿时间:2020-10-21

Therapeutic effect of sitagliptin on the radiation injury of the hematopoietic system in mice
Yuanyang Zhang,Meifang Wang,Yinping Dong,Jing Wu,Xinyue Wang,Wenxuan Li,Deguan Li.Therapeutic effect of sitagliptin on the radiation injury of the hematopoietic system in mice[J].International Journal of Radiation Medicine and Nuclear Medicine,2021,45(8):515-520.
Authors:Yuanyang Zhang  Meifang Wang  Yinping Dong  Jing Wu  Xinyue Wang  Wenxuan Li  Deguan Li
Affiliation:Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300192, China
Abstract: Objective To investigate the therapeutic effect of sitagliptin on hematopoietic system injury in mice after 7 Gy γ-ray irradiation. Methods Fifteen C57BL/6 mice were randomly divided into a control group, an irradiation group, and a sitagliptin+irradiation group by using a randomized block design, with five mice in each group. The mice in the irradiation and sitagliptin+irradiation groups received 7 Gy 137Cs γ-ray total body irradiation. Sitagliptin was administered to the latter via gavage 2 h after the irradiation. The dose was 10 mg/kg, and gavage infusion was continuous. Sitagliptin administration lasted for 7 days. The control and irradiation groups were given the same volume of normal saline. On the 30th day after irradiation, peripheral blood was collected for blood routine examination. After the mice were sacrificed via cervical dislocation, bone marrow cells were collected to determine the numbers of nucleated cells, hematopoietic stem cells (HSC), and hematopoietic progenitor cells (HPC), along with their reactive oxygen species (ROS) levels. The number of colony-forming units granulocyte-macrophage (CFU-GM) clones was also determined. Data between two groups were compared via independent sample t-test. Results Compared with those of the control group, the numbers of bone marrow nucleated cells, white blood cells, red blood cells, platelets, hemoglobin, and hematocrit of the irradiation group were significantly reduced (t=3.476?12.200, all P<0.05). The number and percentage of HSC and HPC were significantly reduced (t=3.174?5.287, all P<0.05). The level of ROS in HSC increased significantly (1980.6±309.3 vs. 3994.5±1119.0, t=3.904, P<0.05). The number of bone marrow cell CFU-GM clones was significantly decreased (66.2±5.3 vs. 30.8±3.9, t=13.240, P<0.05). Compared with the irradiation group, the number of bone marrow nucleated cells ((8.0±1.0)×106 vs. (11.0±0.4)×106, t=4.593, P<0.05) and white blood cells ((3.0±0.2)×109/L vs. (3.9±0.3)×109/L, t=7.020, P<0.05) increased (t=4.593, P<0.05) in the sitagliptin+irradiation group. The number of HPC (33 724.4±10 594.9 vs. 101 637.6±17 240.5, t=5.951, P<0.05) and percentage ((5.6±1.0%) vs. (11.5±3.0)%, t=4.163, P<0.05) also increased. The ROS level in HSC decreased (3994.5±1119.0 vs. 2415.7±122.9, t=2.375, P<0.05), whereas the number of the bone marrow cell CFU-GM clones increased (30.8±3.9 vs. 38.2±4.4, t=2.964, P<0.05). Conclusion Sitagliptin exerts a certain therapeutic effect on hematopoietic system injury in mice after 7 Gy γ-ray irradiation.
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