盐酸雷诺嗪遗传毒性试验研究

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(CP 40mg/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。

Genotoxicity of ranolazine

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...