rhIL-3和GM-CSF对γ线照射猴外周血淋巴细胞损伤的防护作用研究  

Radioprotection of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy γ-rays

作　　者：崔玉芳[1] 杨红[1] 罗庆良[1] 董波[1] 柳晓兰[1] 徐菡[1] 毛秉智[1] 王德文[1] 

机构地区：[1]军事医学科学院放射医学研究所,北京100850

出　　处：《中国危重病急救医学》2004年第1期22-25,共4页Chinese Critical Care Medicine

基　　金：全军"十五"医药卫生科研基金资助项目 (0 1L 0 18;0 1MA0 75 )

摘　　要：目的　观察重组人白细胞介素 3(rh IL 3)和粒细胞巨噬细胞集落刺激因子 (GM CSF)单用与伍用对 3.0 Gyγ线照射猴外周血淋巴细胞损伤的防护作用 ,为造血生长因子用于急性放射病的治疗提供依据。方法　 30只恒河猴随机分为 rh IL 3(2 0和 6 0 μg· kg- 1· d- 1 )、GM CSF(10 μg· kg- 1· d- 1 )、IL 3+GM CSF、照射对照及正常对照共 6个组。γ线全身照射 3.0 Gy连续给药 2 1d后 ,用碱磷酶免疫组织化学法检测 T细胞亚群、Bax和 Bcl 2蛋白 ,用原位末端标记方法检测淋巴细胞凋亡率。结果　 1照射后外周血淋巴细胞数、T细胞及其亚群均显著低于正常组 ,照射对照组 T、TH 和 Ts淋巴细胞分别下降至正常对照组的4 2 %、4 1%和 5 7%。2单独给予 GM CSF和 GM CSF+IL 3后 ,外周血淋巴细胞数量及 T、TH 细胞的降低均受到明显抑制 ,两组的淋巴细胞数均相当于照射对照组的 1.4 8倍 ,GM CSF组 T、TH 细胞分别为对照组的 1.5 7和 1.76倍 ,GM CSF+IL 3组 T、TH 淋巴细胞分别为对照组的 1.4 8和 1.72倍。 3照射后淋巴细胞出现大量凋亡 ;用 GM CSF和 GM CSF+IL 3后能明显抑制照射引起的淋巴细胞凋亡 ,两组淋巴细胞凋亡率分别降低到照射对照组的 4 1%和 4 8%。结论　一定剂量的 GM CSF或 GM CSF+IL 3能明显抑制照射引起的?Objective To observe the radioprotection of recombinant human interleukin-3(rhIL-3), granulocyte-macrophage colony-stimulating factor(GMCSF) and rhIL-3(rhIL-3+GM-CSF) on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy γ-rays, and attempt to provide evidence of cytokines used effectively in the therapy of acute radiation sickness. Methods Thirty rhesus monkey used in the experiment were randomly divided into six groups of rhIL-3 20 μg·kg -1·d -1, 60 μg·kg -1·d -1, GM-CSF 10 μg·kg -1·d -1, IL-3 20 μg·kg -1·d -1+GM-CSF 10 μg·kg -1·d -1, radiation control and normal control. 21 d after whole body γ-irradiation and subcutaneous injection of cytokines, T lymphocyte and its subsets, Bax/Bcl-2 proteins in lymphocytes were determined by immunohistochemical staining with alkaline phosphatase, and lymphocyte apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) technique. Results (1)After irradiation the quantities of peripheral lymphocyte, T cell and its subsets obviously decreased as compared with those of normal controls. For instance, the percentages of lymphocyte, T, T H and Ts cells in radiation control group reduced to 44%, 42%, 41% and 57% of normal controls, respectively. (2)After radiation the reduction of lymphocyte, T, T H and Ts cells were evidently improved by injection of GM-CSF and GM-CSF+ IL-3, The T,T H cells in GM-CSF and GM-CSF+ IL-3 groups were respectively elevated by 1.57 and 1.76 fold, as well as 1.48 and 1.72 fold of radiation controls. (3)A large amount of lymphocyte apoptosis was found after radiation, GMCCSF and GM-CSF+IL-3 treatment could distinctively inhibit abundant lymphocyte apoptosis induced by acute irradiation,the apoptotic rates of lymphocytes in GM-CSF and GM-CSF+IL-3 groups reduced to 41% and 48% respectively when compared with that of radiation controls. Conclusion A definite dose of GM-CSF and GM-CSF+IL-3 could suppress the reduction of lymphocyte, T and T H cells and lymphocyte apoptosis

关 键 词：细胞因子 辐射 BAX蛋白 BCL-2蛋白 T细胞亚群 细胞凋亡 

分 类 号：R818[医药卫生—放射医学] R965[医药卫生—临床医学]