细胞因子联合对4.5 Gyγ射线照射比格犬的实验治疗作用

Experimental therapeutic effect of combined cytokines on beagle dogs exposed to 4.5 Gy γ-rays

目的 观察细胞因子新的组合（rhG-CSF＋rhIL-11＋rhIL-2）对骨髓型急性放射病（ARS）比格犬的治疗作用.方法 以4.5 Gy^60 Coγ射线照射比格犬制备骨髓型ARS动物模型,动物分为照射对照（5只）、综合对症（5只）和综合对症加细胞因子治疗3组（6只）,通过观察动物体征、存活时间、存活数以及动物造血及胃肠道等脏器的恢复情况,分析细胞因子联合治疗效果.结果 4.5 Gy^60 Coγ射线照射后,比格犬出现食欲下降、发热、精神状态差和柏油便等症状,照射对照组动物于照射后2周内全部死亡,平均存活（12.7±1.4）d;综合对症组呈现明显的急性放射病症状,并于照射后第33天死亡1只;而综合对症加细胞因子组动物在45 d观察期内不仅全部存活,临床症状明显改善,且其造血功能及胃、肠道等受损组织基本恢复.结论 在综合对症基础上给予rhG-CSF＋rhIL-11＋rhIL-2组合治疗可以有效地促进4.5 Gy ^60 Coγ射线照射比格犬造血系统功能和胃肠道等重要脏器的恢复,提高受照动物存活数,并改善动物生存质量.

Objective To evaluate the effects of combined administration of recombinant human interleukin-11（rhIL-11）,recombinant human G-CSF（rhG-CSF）and recombinant human interleukin-2 （rhIL-2）on acute radiation sickness（ARS）beagles.Methods Sixteen beagle were irradiated with 4.5 Gy^60 Co γ-rays to establish ARS models,and were divided into irradiation control group,supportive care group and combined cytokines treatment group.After irradiation irradiation control group was given no treatment,the dogs in supportive care group received purely symptomatic treatment,while combined cytokines treatment group received rhIL-11 50μg/（kg·d）and rbG-CSF 10μg/（kg·d）subcutaneously（0-14 d）and rhIL-2 1×1 0^6 U/d（29-43 d）besides symptomatic treatment.Manifestation and characteristics of ARS beagles were observed,and the survival time were recorded.At last,post-mortem examination and histological examination were performed.Results All animals underwent nausea,diarrhea and fever.After irradiation,all animals in irradiation control group died in two weeks,and the mean survival time was 12.7 d,while only one died at 33 d in supportive care group.All dogs in combined cytokine group survived at 45 day after exposure,and their haematopoiesis and gastrointestinal tract were recovered.Conclusions Combination of rhIL-11 ＋ rhG-CSF ＋ rhIL-2 treatment could be significantly effective on ARS beagles irradiated by 4.5 Gy^60 Co γ-rays,which could accelerate injured haemotopoiesis and intestinal tract recovery,increase the survival rate and improve the life quality of animals.