rhIL-11和rhG—CSF对中子照射致小鼠骨髓损伤的治疗作用

Therapeutic effect of rhIL-11 and rhG-CSF on mouse bone marrow injury induced by neutron irradiation

目的探讨rhIL-11和rhG-CSF对中子照射致小鼠骨髓损伤的治疗作用。方法将BALB／c小鼠130只用随机数字表法分为对照组（30只）、照射组（40只）、rhIL-11治疗组（30只）、rhIL-11＋rhG-CSF治疗组（30只），用3．0Gy中子照射，并于照射后给予600μg·kg^-1·d11的rhIL-11和50μg·kg^-1·d11的rhG-CSF，1次/d，共3d；用血细胞自动分析仪、HE染色、AgNOR染色、流式细胞术、免疫组织化学染色和图像分析等，检测小鼠外周血细胞、骨髓病理形态变化、有核细胞计数、AgNOR含量、凋亡与坏死率和Bax蛋白含量的变化。结果照射组和rhIL-11治疗组于照射后6h～3d，小鼠外周血白细胞、骨髓有核细胞计数和AgNOR含量进行性下降，Bax蛋白于造血细胞胞质内呈阳性至强阳性表达，含量进行性增加（F=0．003，P〈0．01）；照射后6h，照射组小鼠造血细胞凋亡与坏死率增加，以坏死为显著；照射后3d，rhIL-11＋rhG-CSF治疗组小鼠的骨髓有核细胞计数和AgNOR含量均增加（F=0．037、0．026，P〈0．05），Bax蛋白含量减少（F=0．018，P〈0．05）；rhIL-11治疗组各指标较照射组差异无统计学意义。结论3．0Gy中子照射可使小鼠骨髓造血功能严重受损，rhIL-11和rhG-CSF对照射后小鼠的造血功能恢复有一定改善作用，联合使用效果优于单独使用。

Objective To explore the therapeutic effect of rhlL-11 and rhG-CSF on mouse bone marrow injury induced by neutron irradiation. Methods 130 male BALB/c mice were irradiated by 3.0 Gy neutron and injected with rhlL-11 at 600 μg·kg^-1·d-1 and rhG-CSF at 50 μg·kg^-1·d^-1 for 3 days after irradiation. The mice peripheral blood cells, bone marrow pathological changes, bone marrow nueleated cell counts, AgNOR content, apoptosis and necrosis rates and Bax protein content were observed by means of blood cells automatic analyzer, HE staining, AgNOR staining, flow cytometry, immunohistochemistry staining and image analysis. Results In the irradiation group and the rhlL-11 group, the mice peripheral blood white blood cells, bone marrow nucleated cell counts and AgNOR content was decreased progressively. The Bax protein was positively or strongly positively expressed in the cytoplasm of the hematopoietie cells and the Box protein content was increased progressively at 6 h, 1 d, 3 d after irradiation. In the irradiation group, the rates of apoptosis and neerosis in the mice hematopoietic ceils were greatly increased and that of necrosis was significant at 6 h after irradiation. In the rhlL-11 ＋ rhG-CSF group, the counts of bone marrow nucleated cell and AgNOR were increased and the Bax protein content was decreased at 3 d after irradiation, while in the rhlL-11 group, the indexes mentioned above were not obviously different compared with those of the irradiation group. Conclusions The mice bone marrow hematopoietie function is seriously damaged by 3.0 Gy neutron irradiation, rhIL-11 and rhG-CSF could improve the mice hematopoiefic function after neutron irradiation, and combination of them is more effective to stimulate the hematopoitic function than either of them alone.