盐酸雷诺嗪遗传毒性试验研究  

Genotoxicity of ranolazine

作　　者：张成梅[1] 史艳秋[1] 宋文延[2] 辛青[3] 尹志圣[1] 刘兆平[1] 

机构地区：[1]山东大学新药评价中心 [2]山东大学医学院诊断学研究所 [3]山东大学校医院,济南250012

出　　处：《山东大学学报（医学版）》2010年第3期66-69,73,共5页Journal of Shandong University:Health Sciences

摘　　要：目的通过研究盐酸雷诺嗪的遗传毒性,评价其药物安全性。方法采用Ames试验、小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验,检测盐酸雷诺嗪的遗传毒性。Ames试验选用直接法和代谢活化法。Ames试验菌株为鼠伤寒沙门氏组氨酸缺陷型菌株TA97、TA98、TA100和TA102,盐酸雷诺嗪在试验中设6个剂量组(5000、2500、1000、500、250和125μg/皿),同时设自发回复突变对照组和阳性对照组;小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验,每项试验设3个盐酸雷诺嗪给药组(222、111和55mg/kg)、阴性对照组(Veh)及阳性对照组(CP40mg/kg)。结果盐酸雷诺嗪在≤5000μg/皿所测剂量范围内,加入和不加入S9的各剂量组对TA97、TA98、TA100和TA102四种菌株的回变菌落数与阴性对照组差异均无统计学意义(P均>0.05),且无剂量反应关系;盐酸雷诺嗪在55～222mg/kg剂量范围内,小鼠骨髓嗜多染红细胞微核数及小鼠精子畸变率与阴性对照组差异无统计学意义(P>0.05)。结论盐酸雷诺嗪在所测剂量范围内,未显示遗传毒性作用。Objective To assess the drug safety of ranolazine by studying its genotoxicity.Methods The Ames test,micronucleus test of mice bone marrow polychromatic erythrocytes and sperm shape abnormality test were used to assess the genotoxicity of ranolazine.The Ames test included the methods of direct measurement and metabolism activation.The strains used in the Ames test were salmonella typhimurium histidine-deficient strain TA97,TA98,TA100 and TA102.Six treatment groups of ranolazine（5 000,2 500,1 000,500,250 and 125 μg/plate） were used during the study,and reverse mutational and positive control groups were set at the same time.There were 3 different administration groups with 222,111 and 55 mg/kg ranolazine,a negative control group（Veh） as well as positive control groups（40 mg/kg） in the micronucleus test of mice bone marrow polychromatic erythrocytes and sperm shape abnormality test assay.Results Compared with the control group,no statistical difference（P〉0.05）in the number of colonies with back mutation per vessel in TA97,TA98,TA100 and TA102 strains treated with ranolazine at≤5 000 μg/plate with or without S9 activation was found.No dosage-dependent relation was found.Moreover,within the dosage of 55-222mg/kg,both the induced micronuclei of mice bone marrow polychromatic erythrocytes and the sperm shape abnormality rate showed no statistical difference（P〉0.05）between ranolazine treated and control groups in mice.Conclusion Ranolazine does not show its genetic toxicity within the dose range that was measured.

关 键 词：盐酸雷诺嗪 AMES试验 微核 精子畸形 遗传毒性 小鼠 

分 类 号：R965.3[医药卫生—药理学] R-332[医药卫生—药学]