新一代重组人粒细胞集落刺激因子(rhG-CSFa)的临床前急性毒性和亚急性毒性研究  

Pre-clinical acute toxicity and sub-acute toxicity study on a novel recombinant human granulocyte-colony stimulating factor a(rhG-CSFa)

作　　者：范洁[1] 丁欣欣[1] 蒋永平[1,2] 

机构地区：[1]中国医学科学院北京协和医学院苏州方舟生物医药研发中心,江苏苏州215126 [2]苏州方舟基因药业有限公司,江苏苏州215126

出　　处：《复旦学报（医学版）》2012年第1期25-30,共6页Fudan University Journal of Medical Sciences

基　　金：国家"重大新药创制"科技重大专项基金项目(2009ZX09102-250);江苏省高技术研究计划项目医药部分(BG20070605)~~

摘　　要：目的研究新一代重组人粒细胞集落刺激因子(recombinant human granulocyte-colony stimulatingfactor a,rhG-CSFa)在不同给药途径和时间下的急性和亚急性毒性。方法 6周龄雌雄各半昆明种小鼠80只,随机均分8组进行急性毒性实验:阴性对照组(2组)注射等量生理盐水,其余6组分别由皮下或静脉注射34、345、3 450μg/kg的rhG-CSFa,连续观察生理状态10天。另取6周龄雌雄各半昆明种小鼠50只,随机均分5组进行亚急性毒性实验。对照组注射等量生理盐水,其余各组每次分别皮下注射1.1、11.5、115、1 150μg/kg的rhG-CSFa,连续3周每24h给药一次并观察其生理状态。末次给药24h后处死小鼠,进行解剖学检查,并分别作白细胞计数及制作血涂片和骨髓涂片镜检。结果 (1)急性毒性实验小鼠无明显毒性作用及不良反应。实验组与对照组相比无明显体重差异(P>0.05),个别组体重偏低但生理功能未现异常,10日内未见其死亡;(2)亚急性毒性实验小鼠无明显毒性作用及不良反应,实验组白细胞数量显著增加(P<0.01)。结论 rhG-CSFa对小鼠无明显急性和亚急性毒性作用。Objective To assess the severity of the acute toxicity and sub-acute toxicity of a novel recombinant human granulocyte-colony stimulating factor a（rhG-CSFa） in mice and the dose-effect relationship. Methods Total 80 mice（equal numbers of male and female） were randomized into eight groups for the acute toxicity study：six groups were subcutaneously or intravenously injected with rhG-CSFa at 34,345,and 3 450 μg/kg,respectively,and two groups were injected with normal saline as the control.The physical status and body weight were monitored for the next 10 days.Another 50 mice（equal numbers of male and female） were randomized into five groups for the sub-acute toxicity study： four groups were subcutaneously injected with rhG-CSFa at 1.1,11.5,115,and 1 150 μg/kg,respectively,and the other group was treated with normal saline as the control.The mice received injections for 3 weeks.The physical status and body weight were monitored.The mice were sacrificed after the last rhG-CSFa administration.The numeration of leukocyte,bone marrow smear and blood smear were performed for each mouse. Results Acute toxicity study indicated that no significant acute toxicity was observed in mice received rhG-CSFa administration.There was no significant difference of weight between the control and the treatment groups（P0.05）.Further study of sub-acute toxicity revealed that the absolute number of granular leukocytes in mice from three treatment groups were higher compared with the control group（P0.01）,and the increase of granular leukocytes was rhG-CSFa dose-dependent.No significant abnormalities were observed in this study. Conclusions No significant toxicity was observed in mice received rhG-CSFa administration in the acute and sub-acute toxicity studies.

关 键 词：重组人粒细胞集落刺激因子(rhG-CSFa) 小鼠 急性毒性 亚急性毒性 

分 类 号：R994.1[医药卫生—毒理学]