重组人角质细胞生长因子-2对兔眼的长期毒性作用  

Study on long-term toxicity of recombination human keratinocyte growth factor-2 in rabbit eyes

作　　者：胡浩[1,2] 项琪[1] 曲红艳[1,2] 贾旭[3] 黄亚东[1,2] 

机构地区：[1]暨南大学医药生物技术研究开发中心,广东广州510632 [2]广东暨大基因药物工程研究中心有限公司,广东广州510632 [3]湖南大学化学化工学院,湖南长沙410000

出　　处：《沈阳药科大学学报》2016年第5期379-384,390,共7页Journal of Shenyang Pharmaceutical University

基　　金：广东省科技计划项目(2012B080702004);广东省教育部产学研结合项目(2011B090400323);国家重大新药创制项目(2012ZX09103301-034)

摘　　要：目的观察重组人角质细胞生长因子-2(recombination human keratinocyte growth factor-2,rhKGF-2)对兔眼的长期毒性。方法 32只新西兰白兔,随机分为对照组及高(2 000 mg·L-1)、中(500 mg·L-1)、低(125 mg·L-1)剂量组,每组8只,连续滴眼给药重组人角质细胞生长因子-2,每天6次,每2 h给药1次,单眼给药0.1 m L,给药4周,停药后恢复2周。观察一般药物反应及眼部症状,检测动物血液学、血液生化学和组织病理学等指标。结果除了中高剂量组分别有7例和8例眼部有少量类似眼屎的黏性分泌物及高剂量组有3例出现睑结膜充血呈鲜红色外,其他动物眼部未见与给药相关的明显异常变化;体质量、进食量、体温、心电图、尿液、血液学、凝血、血液生化学、骨髓细胞、脏器质量、脏器系数和病理学检查均未见明显与给药相关的异常变化。结论本试验选用3个剂量分别为有效剂量浓度的5、20和80倍,并未对新西兰白兔产生明显毒性,说明该剂量对新西兰白兔眼部用药是安全的。Objective To study the long-term toxicity of rh KGF-2 in rabbit eyes. Methods Thirty-two NewZealand white rabbits were randomly divided into four groups,i. e. control group,high dose（ 2 000 mg·L- 1）,medium dose（ 500 mg·L- 1）,lowdose（ 125 mg·L- 1） group respectively. 0. 1 m L of rh KGF-2 eye drop with different concentration was administered to rabbit eye by continuous dropping with the frequency of once every two hours and 6 times a day for 4 weeks. After 2 weeks of recovery without administration,general drug reaction and eye symptoms were observed,and animal hematology,blood chemistry,histopathology and other indicators were also detected. Results No visible changes in the eye was observed during the course of administration,except a small amount of eye discharge-like sticky mucus secretions was observed in 7 rabbits in medium dose group and 8 rabbits in high dose group,and bright red conjunctiva congestion was observed in3 cases in high dose group. Body weight,food intake,body temperature,ECG,urine,hematology,coagulation,blood chemistry,bone marrowcells,organ weight,organ coefficient and pathological examination also showed no significant changes associated with the administration. Conclusions Three doses used in this experiment were 5,20 and 80 times higher than the effective dose for NewZealand white rabbits,and they did not cause any significant toxicity,which indicated that the dose of rabbit eye medication is safe.

关 键 词：重组人角质细胞生长因子-2 长期毒性 血液生化学 组织病理学 

分 类 号：R988.1[医药卫生—药品] R779.12[医药卫生—药学]