rHuEPO、rHuGM-CSF对大鼠芥子气全身中毒疗效的初步评价

Evaluation of rHuEPO and rHuGM-CSF in the Treatment of Sulfur Mustard (bis-2-Chloroethyl Sulphide) Induced Toxicity in SD Rats

目的 :评价重组人红细胞生成素 (rHuEPO)、重组人粒细胞 -巨噬细胞集落刺激因子 (rHuGM CSF) ,对SD大鼠芥子气全身中毒的治疗作用。方法 :本实验以SD大鼠为动物模型 ,4mg/kg体重芥子气皮下注射为中毒剂量。治疗组动物在中毒后 0 .5h即皮下注射治疗药物 ,其中rHuEPO的剂量为 30 0IU/kg体重 ,第 1天和第 3天各 1次 ;rHuGM CSF的剂量为15 μg/kg体重 ,连续应用 5d。通过观察 1周内动物腹泻率、死亡率、体重变化、血常规指标变化、骨髓细胞增生程度和细胞学分类等来评价药物疗效。结果 :和中毒对照组相比 ,药物治疗组的腹泻率、死亡率、动物体重、血常规指标以及骨髓细胞学分类等均无显著差异。但治疗组在中毒后第 8天的血常规中红细胞 (RBC)和血红蛋白 (HGB)已上升到和正常对照组无明显差异 ,而中毒对照组却仍然显著低于正常对照组。另外 ,虽然统计学上无显著差异 ,但骨髓细胞分类显示治疗组中单核细胞系比例和红细胞系比例也较中毒对照组有升高趋势。结论 :SD大鼠芥子气中毒后 ,只应用rHuEPO和rHuGM CSF进行药物治疗 ,虽然能一定程度上刺激骨髓红细胞系和单核细胞系的生长 ,但对其他细胞系的刺激作用不明显 ,而且反而可能由于其副作用使动物的腹泻率和死亡率升高。因此在芥子气全身中毒的综合治疗方案中 ,

Objective: To evaluate the therapeutic effects of recombinant human erythropoietin (rHuEPO) and recombinant human granulocyte macrophage colony stimulating factor (rHuGM CSF) on sulfur mustard (SM) induced toxicity in SD rats. Methods: SD Rats were used as the animal model. Half on hour after subcutaneously injected with 4 mg/kg (body weight) of SM, the rats of the treatment group were subcutaneously injected with 300 IU/kg (body weight) of rHuEPO (on the 1st and 3 rd day) and 15 μg/kg(body weight) of rHuGM CSF (for 5 days). Diarrhoea rate and death rate, changes of body weight, general examination of blood, cytological examination of bone marrow in a week were observed to evaluate the therapeutic effects of the drugs. Results: All the results showed that there was no statistically significant difference between the treatment group and the SM control group. But in the general examination of blood on the 8 th postexposure day, the red blood cell count (RBC) and the hemoglobin (HGB) of the treatment group had increased to a degree which had no statistical difference from the normal group. While at the same time, the results of SM control group were significantly less than those of the normal group. Additionally, the cytological classification of the marrow showed that the mononuclear cell and the erythrocyte of the treatment group had increased although no statistical difference existed, compared with the SM control group. Conclusion: The use of rHuEPO and rHuGM CSF after SM expoure can stimulate the growth of the erythrocyte and the mononuclear cell of the bone marrow in SD rats. But the effects on other marrow cells are not evident. Meanwhile, rHuEPO and rHuGM CSF may increase the diarrhoea rate and the death rate in animals by their side effects. Therefore, rHuEPO and rHuGM CSF can only be used as assistant drugs and should be combined with other therapeutic drugs in future SM treatment.