ZHAO Jian-zhi,LI Ming,XING Shuang,HU Zhi-qing,XIONG Guo-lin,XIE Ling,OU Hong-ling,HUANG Hai-xiao,ZHAO Zhen-hu,WANG Ning,WANG Jin-xiang,MIAO Jing-cheng,ZHU Nan-kang,ZHANG Xue-guang,CONG Yu-wen,ZHANG Ri,LUO Qing-liang.Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles[J].Chinese Journal of Radiological Medicine and Protection,2010,30(3):247-251
Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles
Received:December 24, 2009  
DOI:10.3760/cma.j.issn.0254-5098.2010.03.004
KeyWords:rhG-CSF  rhIL-11  rhIL-2  Hematopoietic injuries  Beagles
FundProject:国防科工委"十一五"核科学基础研究重点项目(A3620060130)
Author NameAffiliationE-mail
ZHAO Jian-zhi The First Affiliated Hospital of Soochow University, Suzhou 215006, China  
LI Ming 军事医学科学院放射与辐射研究所  
XING Shuang 军事医学科学院放射与辐射研究所  
HU Zhi-qing 苏州大学医学部  
XIONG Guo-lin 军事医学科学院放射与辐射研究所  
XIE Ling 军事医学科学院放射与辐射研究所  
OU Hong-ling 第二炮兵总医院  
HUANG Hai-xiao 军事医学科学院放射与辐射研究所  
ZHAO Zhen-hu 军事医学科学院放射与辐射研究所  
WANG Ning 军事医学科学院放射与辐射研究所  
WANG Jin-xiang 苏州大学医学部  
MIAO Jing-cheng 苏州大学医学部  
ZHU Nan-kang 苏州大学医学部  
ZHANG Xue-guang 苏州大学医学部  
CONG Yu-wen 军事医学科学院放射与辐射研究所  
ZHANG Ri The First Affiliated Hospital of Soochow University, Suzhou 215006, China  
LUO Qing-liang 军事医学科学院放射与辐射研究所 luoqingliang52@ yahoo. com. cn 
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Abstract::
      Objective To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy 60Co γ-rays irradiation in beagles, and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS). Methods 16 beagles were given 4.5 Gy 60Co γ-rays total body irradiation, and then randomly assigned into irradiation control group, supportive care group and cytokines group. In addition to supportive care, recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human interleukin-11 (rhIL-11) and recombinant human interleukin-2 (rhIL-2) were administered subcutaneouly to dogs in cytokines group. Peripheral blood hemogram was examined once every two days. Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation. Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation, the population of all kinds of cells in peripheral blood declined sharply. WBC nadir was elevated (1.04?109/L, but 0.28?109/L and 0.68?109/L for the irradiation control group and the supportive care group separately), the duration of thrombocytopenia was shortened (24 days, but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokines treatment in combination. The colony forming efficiency of haemopoietic stem cells (HSCs) in bone marrow and peripheral blood decreased obviously 1 d post irradiation, but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment. Hematopoietic cells disappeared in bone marrow of animals in irradiation control group, but hematopoietic functions were recovered after cytokines were administrated. Conclusions RhG-CSF, rhIL-11 and rhIL-2 used in combination could elevate WBC nadir, accelerate the recovery of leukocytes, platelets and red blood cells and promote the proliferation, differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation, eventually restore the hematopoietic function. Hence, combination of rhG-CSF, rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.
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