新型降血糖化合物G004的遗传毒性与生殖毒性研究  

Study on Genotoxicity and Reproductive Toxicity of New Hypoglycemic Compound G004

作　　者：蔡鸣[1] 侯艳[1] 乔红群[2] 刘晶[1] CAI Ming;HOU Yan;QIAO Hongqun;LIU Jing(Jiangsu Institute of Materia Medica,Nanjing 210009,China;School of Pharmacy,Nanjing University of Technology,Nanjing 211816,China)

机构地区：[1]江苏省药物研究所,南京210009 [2]南京工业大学药学院,南京211816

出　　处：《中国药房》2018年第22期3078-3082,共5页China Pharmacy

基　　金：江苏省科技厅政策引导类计划(产学研合作)项目(No.BY2016005-10)

摘　　要：目的:研究新型降血糖化合物G004的遗传毒性与生殖毒性。方法:分别采用Ames试验(鼠伤寒沙门氏菌突变株回复突变试验)、CHL细胞(中国仓鼠肺成纤维细胞)染色体畸变试验、小鼠骨髓微核实验考察G004的遗传毒性;采用大鼠胚胎-胎仔发育毒性实验,在大鼠妊娠第6~15天连续灌胃给药G004(剂量分别为100、300、900 mg/kg),考察其对孕鼠体质量和摄食量、胚胎形成以及胎鼠生长发育等的影响,评价其生殖毒性。结果:遗传毒性方面,G004的Ames试验、CHL细胞染色体畸变试验和小鼠骨髓微核实验结果均为阴性;生殖毒性方面,G004各剂量组孕鼠均无明显毒性反应,100、300 mg/kg剂量组胎鼠生长发育正常,仅900mg/kg剂量组出现吸收胎数增加及胎鼠骨骼发育迟缓。结论:G004无明显遗传毒性;剂量≤900 mg/kg时对怀孕大鼠母体无毒性作用,剂量≤300 mg/kg时对大鼠子代无致畸作用。OBJECTIVE:To study the genotoxicity and reproductive toxicity of new hypoglycemic compound G004.METHODS:The genotoxicity of G004 was investigated by Ames trial(reverse mutation test of Salmonella typhimurium mutant),CHL cell(Chinese hamster lung fibroblasts)chromosomal aberration test and mice bone marrow micronucleus test.In embryo-fetal development toxicity test,pregnant rats were given medicine intragastrically during 6-15 days of pregnancy(G004 dose of 100,300,900 mg/kg).The effects of G004 on body weight and food intake of pregnant rats,embryo formation and fetal rat growth and development were investigated to evaluate reproductive toxicity of G004.RESULTS:The negative genotoxicity results were obtained in Ames trial,CHL cell chromosomal aberration test and mice bone marrow micronucleus test.In respect of reproductive toxicity,there was no obvious toxic reaction in pregnant rats of G004 different dose groups,and rat embryos developed normally in G004 100,300 mg/kg groups.Only resorption number increased and rat embryos developed slowly in 900 mg/kg group.CONCLUSIONS:G004 shows no obvious genotoxicity.When the doses are not more than 900 mg/kg,G004 has no toxic effect on rat;when the doses are not more than 300 mg/kg,G004 has no teratogenic effect on rat offspring.

关 键 词：降血糖药 G004 遗传毒性 生殖毒性 胚胎 发育 

分 类 号：Q355[生物学—遗传学]