重组小鼠白细胞介素12(rmIL-12)的辐射保护作用和对骨髓造血功能的影响

Effect of recombinant murine Interleukin 12(rmIL-12) on radiation protection and bone marrow hematopoietic function

目的重组小鼠白细胞介素12(rmIL-12)对γ-射线照射后小鼠存活状况、骨髓造血功能和体外小鼠骨髓间充质干细胞存活的影响。方法 60只小鼠按体质量随机分为照射对照组、阳性对照组和rmIL-12组(200 ng/只),每组20只,雌雄各半,用60Co射线照射源,小鼠全身照射8.0 Gy用于存活率的实验研究;30只雌性小鼠,分为同样3组,全身4.0 Gy照射用于对造血功能影响的研究。均在照射前24 h和1 h各给药1次,照射后每天给药1次,连续7 d,给药途径为皮下注射。噻唑蓝(MTT)比色法观察在不同辐射剂量下rmIL-12对体外培养的骨髓间充质干细胞生存的影响。结果 rmIL-12可明显提高8.0 Gy60Coγ射线照射小鼠30 d存活率,使生存曲线(Kaplan Meier曲线)显著增高及右移;在60Coγ射线辐射剂量为4.0 Gy时,rmIL-12对小鼠外周血白细胞(WBC)、血小板(PLT)和网织红细胞(RET)计数增高和恢复提前,骨髓DNA含量也显著高于对照组;同时受试物终浓度在0.125～32 ng/ml范围内时,体外可观察到rmIL-12对60Coγ射线不同剂量辐射的小鼠骨髓间充质干细胞(MSCs)的生存有保护效应。结论 rmIL-12能够提高60Coγ射线辐射下小鼠的存活率以及促进造血功能的恢复,对体外培养的小鼠骨髓间充质干细胞的生存有保护作用。

Objective To study the effect of recombinant mouse interleukin-12（rmIL-12） on survival and bone marrow hematopoietic function of gamma-ray irradiated mice. Methods Mice were randomly divided into three groups according＇to weight： irradiation control group, positive control group and rmIL-12 treatment group （200 ng/mouse）. Sixty mice, twenty in each group （ male ： female = 1 ： 1 ）, were used to study the survival rate after total body irradiation （TBI） in 8.0 Gy while thirty female mice, ten in each group, were used to study the effect on hematopoietic function after TBI in 4.0 Gy. All mice were administrated 24 h and 1 h before the delivery of irradiation time and after irradiation of medication, once a day, for 7 days, via subcutaneous injection. The protection effect on survival in mice bone marrow mesenchymal stem cells （MSCs） cultured in vitro was observed in different irradiation doses. Results In 6o Co gamma-ray radiation dose for 8.0 Gy, rmIL-12 obviously increased the survival rate, lifted and right-shifted its survival curve （Kaplan-meier curve）after TBI in mice. In 6oCo gamma-ray radiation dose for 4.0 Gy, the number of white blood ceils, platelets and reticulocytes in peripheral blood was increased by rmIL-12, and the content of DNA in bone marrow was obviously higher than in control group. Meanwhile, the final concentration of rmIL-f2 ranged from 0. 125 ng/ml to 32 ng/ml. Protection effect on the MSCs survival in different doses was observed in vitro. Conclusion rmIL-12 can increase the survival rate and accelerate the recovery of hematopietic function after total body irradiation （TBI） in mice, and also has the protective effect in the surviv- al of vitro cultured MSCs.