照前给予去甲肾上腺素增强电离辐射对小鼠血小板生成能力的损伤作用

发布时间：2018-03-02 06:05

本文关键词： 去甲肾上腺素血小板辐射损伤　出处：《第三军医大学学报》2017年08期 　论文类型：期刊论文

【摘要】：目的探讨去甲肾上腺素(norepinephrine,NE)对电离辐射(ionizing radiation,IR)损伤小鼠血小板水平的影响作用。方法 80只健康雄性C57BL/6小鼠按完全随机的方法分为未辐射对照组(PBS)、未辐射给药组(NE)、辐射对照组(PBS+IR)和辐射给药组(NE+IR),每组20只小鼠。给药组给予腹腔注射NE(1.5 mg/kg),对照组给予腹腔注射等体积PBS,处理24 h后辐射组进行全身一次性6 Gyγ射线照射。辐射后不同时间点尾静脉采血检测小鼠血常规,并于辐射后第9天使用HE染色观察小鼠骨髓变化,流式细胞术分析小鼠骨髓造血干细胞(hematopoietic stem cells,HSCs)比例变化以及巨核细胞凋亡、周期的变化。结果未辐射时,NE组小鼠给药后3~10 d血小板数量显著高于PBS组(P0.05);HSCs占骨髓Lineage细胞的比例:NE组为(1.44±0.08)%,PBS组为(1.05±0.10)%,两组差异具有统计学意义(P0.05);同时,NE也具有促进离体培养小鼠HSCs的增殖,并且在药物浓度100 nmol/m L的范围内具有剂量效应依赖关系;HE染色显示,NE组的骨髓有核细胞和巨核细胞数目显著高于PBS组(P0.05);巨核系祖细胞周期的结果显示,NE组G0/G1期细胞百分比减少约(12.10±3.12)%、S期细胞比例增加约(8.78±1.05)%,与PBS组比较差异具有统计学意义(P0.05)。辐射后,NE+IR组小鼠7~25d血小板数量低于PBS+IR组(P0.05);HSCs占骨髓Lineage细胞的比例:NE+IR组为(0.07±0.01)%,PBS+IR组为(0.27±0.03)%,两组差异具有统计学意义(P0.05);HE染色结果显示,NE+IR组的骨髓有核细胞和巨核细胞数目显著低于PBS+IR组(P0.05);巨核祖细胞凋亡结果显示,NE+IR组凋亡率为(84.46±5.09)%,明显高于PBS+IR组[(54.18±3.18)%,(P0.05)]。结论去甲肾上腺素使造血干细胞、巨核祖细胞过度活化,从而增加了小鼠对电离辐射的敏感性,使血小板生成减少。
[Abstract]:Objective to investigate the effect of norepinephrine (NE) on platelet level in mice induced by ionizing radiation (IRR). Methods 80 healthy male C57BL / 6 mice were randomly divided into control group (n = 80) and control group (n = 30). 20 mice in each group were given intraperitoneal injection of NE(1.5 mg / kg, while the control group was given intraperitoneal injection of NE(1.5 of the same volume. After 24 hours of treatment, the radiation group was irradiated with a single dose of 6 Gy 纬-ray. Blood samples from caudal vein were collected at different time points to detect blood routine in mice. The changes of bone marrow in mice were observed by HE staining on the 9th day after irradiation. The percentage of hematopoietic stem cells and the apoptosis of megakaryocytes were analyzed by flow cytometry. Results the number of platelets in the NE group was significantly higher than that in the PBS group on the 10th day after administration. The percentage of Lineage cells in bone marrow cells in the group of 1: 1. 44 卤0. 08 was 1.44 卤0. 08. The difference between the two groups was statistically significant (P 0. 05), and the ratio of NE to Lineage cells in the group was significantly higher than that in the control group (P 0. 05 and P 0. 05), and the ratio of NE to Lineage cells in the control group was significantly higher than that in the control group (1. 44 卤0. 08). The proliferation of HSCs in vivo, He staining showed that the number of bone marrow nucleated cells and megakaryocytes in the NE group was significantly higher than that in the PBS group, and the results of megakaryocyte progenitor cell cycle showed that the G0 / G1 phase was fine in the NE group. The percentage of cells in S phase decreased by about 12.10 卤3.12 and increased by 8.78 卤1.05, which was significantly different from that in PBS group (P 0.05). The platelet count of mice in NE IR group was lower than that in PBS IR group on 725 days after irradiation, and the percentage of Lineage cells in bone marrow cells in PBS IR group was 0.07 卤0.01%, which was 0.27 卤0.03T in PBS IR group. The results of HE staining showed that the number of nucleated cells and megakaryocytes in the NE IR group was significantly lower than that in the PBS IR group, and the apoptotic rate of megakaryocyte progenitor cells in the NE IR group was 84.46 卤5.09, which was significantly higher than that in the PBS IR group [54.18 卤3.18P0.05]. Conclusion norepinephrine can induce hematopoietic stem cells, Megakaryocyte progenitor cells were over-activated, which increased the sensitivity of mice to ionizing radiation and reduced platelet formation.
【作者单位】：第三军医大学军事预防医学院全军复合伤研究所创伤、烧伤与复合伤国家重点实验室重庆市纳米医药工程技术研究中心;
【基金】：国家自然科学基金面上项目(81573084) 重庆市科技创新领军人才支持计划(CSTCKJCXLJRC06)~~
【分类号】：R730.5

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