大鼠肌内注射重组人碱性成纤维细胞生长因子的毒性研究  

The toxicity of recombinant human basic fibroblast growth factor(rhbFGF)in rats

作　　者：高月[1] 吕秋军[1] 陈鹏[1] 陶来宝[1] 谭洪玲[1] 马增春[1] 丁林茂[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：《中国新药杂志》2001年第1期32-34,共3页Chinese Journal of New Drugs

摘　　要：目的 :观察大鼠重组人碱性成纤维细胞生长因子 (rhbFGF)的毒性反应 ,提供毒性反应的靶器官及其损伤的可逆性 ,确定无毒反应剂量 ,为临床安全用药提供参考。方法 :实验分 4组 ,即溶剂对照组及 8,32和 12 8μg/L给药组 ,各组试验动物分别在 15 ,30d和停药后 30d活杀 ,中和抗体检测在 2 0和 2 5d各活杀 6只动物。分别观察外周血各项指标 ,血清生化 10项指标及血清中大鼠抗人rhbFGF抗体滴度等。结果 :12 8μg/ (kg·d)肌内注射30d ,其主要毒性表现为外周血红细胞数和血红蛋白含量降低。病理检查显示 ,肾小球内细胞核大的足细胞数目增多 ,胞体增大 ,胞浆内出现大小不等的空泡 ,胸骨皮质及骨小梁较对照组略有增粗等。结论 :12 8μg/ (kg·d)是rhbFGF的明显中毒剂量 ,主要毒性靶器官是肾脏。 32 μg/ (kg·d)剂量可产生轻度的毒性反应 ,而 8μg/ (kg·d)剂量无明显毒性作用 。Objectives:In order to determine the non toxicic dose of rhbFGF,its toxicity in rats was studied.Methods;Wistar rats were divided into 4 groups,including 3 active groups[receiving 8,32 or 128μg/(kg·d) rhbFGF respectively]and 1 control group.After 30 days,the peripheral blood parameters,10 biochemical parameters,and the rats'serum titer of rhbFGF antibody were observed.Results:After intramuscular injection of 128μg/(kg·d) rhbFGF for 30 days,the peripheral red cell counting and hemoglobin content were decreased.Pathological examination indicated that the glomerular podocytes increased and body cells enlarged,vacuoles of various sizes appeared in cytoplasm and the sternum cortex and bone trabecula were thicked slightly in comparison with control.Conclusions:The non toxicic and safe dose for rhbFGF is 8μg/(kg·d).

关 键 词：重组人碱性成纤维细胞生长因子 大鼠 安全性评价 毒性研究 

分 类 号：R965.3[医药卫生—药理学]