中文摘要：

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（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。

英文摘要：

Objective To study the effect of norepinephrine （NE） on ionizing radiation （IR）-induced thrombocytopenia in mice and its possible mechanism. Methods Eighty normal C57BL/6 mice （8~10 weeks old） were randomly allocated into 4 equal groups and subjected to intraperitoneal injection of PBS or NE with or without total body irradiation （TBI） at 6 Gy for 24 h after the injection. At different time points following TBI, blood samples were collected from the tail vein of the mice for measuring platelet count and other routine blood biochemical parameters. The changes of the bone marrow cellularity were examined with HE staining at 9 d after TBI, and the changes in apoptosis of MO7e cells, cell cycle of megakaryocytic progenitors, and the frequency of LSK cells in mouse-derived Sca1＋ cells and in mice exposed to IR were analyzed with flow cytometry. Results As compared with those in PBS group, the platelet count in 3～10 d after injection and the frequency of HSCs of Lineage cells in murine bone marrow increased significantly [（1.44±0.08）% vs （1.05±0.10）%, P〈0.05]. In addition, NE treatment significantly promoted the proliferation of HSCs in vitro, which showed a dose response relationship（≤100 nmol/mL concentration）. Further more, HE staining showed that the numbers of bone marrow nucleated cells and megakaryocytes were significantly higher in NE group than those in PBS group. Moreover, （12.10±3.12）% of G0/G1 phase cells in the progenitor cells significantly decreased and （8.78±1.05）% of S phase cells in the progenitor cells significantly increased in NE group （P〈0.05）. Effects were opposite when mice or cells were subjected to TBI after NE administration：the platelet count during the 7th～25th days and the number of bone marrow nucleated cells（P〈005）, the frequency of HSCs of Lineage-cells in murine bone marrow [（0.07±0.01）% vs （0.27±0.03）%, P〈0.05], and the number of bone marrow nucleated cells and megakaryocytes in NE＋IR grou