论文部分内容阅读
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(P<0.05);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(P<0.05);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(P<0.05);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(P<0.05)。辐射后,NE+IR组小鼠7~25d血小板数量低于PBS+IR组(P<0.05);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(P<0.05);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(P<0.05);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)%,(P<0.05)]。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。
Objective To investigate the effects of norepinephrine (NE) on platelet levels in mice exposed to ionizing radiation (IR). Methods Eighty healthy male C57BL / 6 mice were randomly divided into four groups: control group (PBS), non-radiation group (NE), radiation control group (PBS + IR) and radiation group (NE + IR), 20 mice per group. In the control group, an intraperitoneal injection of NE (1.5 mg / kg) was given to the rats in the treatment group. An equal volume of PBS was injected into the control group and a one-time whole-body 6 Gy γ ray irradiation was performed 24 h after the irradiation. Blood samples were collected from the caudal vein at different time points after irradiation. The changes of bone marrow of mice were observed by HE staining on day 9 after radiation. The proportion of hematopoietic stem cells (HSCs) in bone marrow was analyzed by flow cytometry Megakaryocyte apoptosis, cycle changes. The results showed that the number of platelets in NE group was significantly higher than that in PBS group at 3 ~ 10 d after administration (P <0.05). The proportion of HSCs in lineage cells was (1.44 ± 0.08)% in NE group and (1.05 ± 0.10)%, the difference between the two groups was statistically significant (P <0.05); at the same time, NE also could promote the proliferation of HSCs in vitro and dose-effect in the range of drug concentration of 100 nmol / m L (P <0.05). The results of HE staining showed that the number of bone marrow nucleated cells and megakaryocytes in NE group was significantly higher than that in PBS group (P <0.05). The results of megakaryocyte progenitor cell cycle showed that the percentage of cells in G0 / G1 phase decreased by about 12.10 ± 3.12)%, and the proportion of cells in S phase increased by (8.78 ± 1.05)%, which was statistically significant compared with PBS group (P <0.05). After irradiation, the number of platelets in NE + IR group was lower than that in PBS + IR group (P <0.05). The proportion of HSCs in Lineage cells was (0.07 ± 0.01)% in NE + IR group and (0.27 ± 0.03)%, the difference between the two groups was statistically significant (P <0.05). HE staining showed that the number of bone marrow nucleated cells and megakaryocytes in NE + IR group was significantly lower than that in PBS + IR group ). The apoptosis of megakaryocyte progenitor cells showed that the apoptotic rate in NE + IR group was (84.46 ± 5.09)%, which was significantly higher than that in PBS + IR group (54.18 ± 3.18)% (P <0.05). Conclusion Norepinephrine over-activation of hematopoietic stem cells and megakaryocyte progenitor cells increased the sensitivity of mice to ionizing radiation and reduced platelet production.