白细胞介素12早期干预对急性放射病小鼠的治疗作用  

Therapeutic effect of rmIL-12 early administrated on acute radiation sickness produced by γ-rays irradiation in mice

作　　者：王利[1,2] 翟瑞仁 逄朝霞 张超 余长林[1] 

机构地区：[1]军事医学科学院附属医院血液科,北京100071 [2]解放军第四〇一医院崂山分院血液肿瘤科,山东青岛266101

出　　处：《现代肿瘤医学》2012年第8期1548-1551,共4页Journal of Modern Oncology

基　　金：全军科技攻关课题资助项目(编号:N008g157)

摘　　要：目的:研究重组鼠白细胞介素12(rmIL-12)早期干预对γ射线急性放射病小鼠的治疗作用,并与重组鼠血小板生成素(rmTPO)的辐射防护作用进行比较。方法:42只BALB/c小鼠均给予60Coγ射线6.0Gy一次全身照射后随机分为照射对照(对照)、rmIL-12治疗和rmTPO治疗3组。rmIL-12治疗组小鼠于照射后1h及此后每3d一次分别腹腔注射rmIL-12 20μg/(kg.d),共5次;rmTPO治疗组小鼠于照射后0.5和24h分别皮下注射rmTPO 15μg/kg;对照组给予等体积的无菌PBS。2次/d观察小鼠一般情况,3d检测1次外周血细胞数,分别于照射后14d和28d收集骨髓细胞进行集落培养。结果:rmIL-12治疗组小鼠一般情况较对照组改善,外周血中血小板(PLT)下降速度明显慢于对照组,PLT恢复时间较对照组明显提前(11d vs 14d),且PLT最低值明显高于对照组(18.9%vs 8.1%,P<0.05)。rmIL-12治疗组PLT恢复速度稍快于rmTPO治疗组,但差异无统计学意义(P>0.05)。照射后14和28d骨髓有核细胞集落培养结果提示rmIL-12治疗组CFU-Mix明显高于对照组(P<0.01),与rmTPO治疗组差异无统计学意义(P>0.05)。结论:rmIL-12可明显促进急性放射病小鼠造血功能恢复,对巨核系的恢复作用与rmTPO相当,有望开发成安全有效的新型辐射防治药物。Objective ：To study the therapeutic effect of recombinant murine interleukin 12 （rmlL - 12）early ad- ministrated on the mice irradiated by γ - rays, and compared its radioprotective effect with recombinant murine throm- bopoietin （rmTPO）. Methods： Forty -two BALB/c mice were given 6.0Gy 60Co γ-rays total body irradiation and randomly assigned into irradiation control group ,rmlL- 12 treatment group and rmTPO treatment group. 20μg/kg of rmlL - 12 was administrated intraperitoneally 1 hour following irradiation, and was administrated every 3 days after ir- radiation for four times in rmlL - 12 treatment group. 15μg/kg of rmTPO was administrated subcutaneously half and 24 hours following irradiation in rmTPO treatment group. The general conditions of mice were observed twice a day, the changes in body weight, peripheral blood cell counts were examined once every three days, bone marrow ceils were collected to perform colony cultivation on the 14th and 28^th day after irradiation. Results： The general conditions of mice in rmlL - 12 treatment group were better than those of irradiation control group. Compared with the irradiation control group, the decline speed of platelet was significantly slower than that of control group, rmlL - 12 treatment sig- nificantly promoted platelet recovery, resulting in less profound nadirs （ 18.9% vs 8.1% , P 〈 0.05 ） and rapid recover- y to normal levels（ 11 days vs 14 days）. The platelet recovery speed in rmlL- 12 treatment group was as fast as that of rmTPO treatment group. Semi - solid bone marrow cell culture also demonstrated that rmlL - 12 could stimulate bone marrow cells to form more CFU - Mix than those of the irradiation control group in vitro on 14th and 28＇h after ir- radiation（P 〈 0.0l）, there was no significant difference between rmlL- 12 and rmTPO treatment group. Conclu- sion： RmlL- 12 can significantly accelerate the recovery of hematopoietic function in acute radiation sickness mice, its radioprotective effect is as good as rmTP

关 键 词：白细胞介素12 血小板生成素 急性放射病 造血损伤 Γ射线 小鼠 

分 类 号：R73-362[医药卫生—肿瘤]