摘要:
Objective To study mouse micronucleus test of rabeprazole sodium administered orally,evaluation dextral rabeprazole sodium on chromosome damage in animals to predict their genetic toxicity. Methods Healthy male BALB / c mice were 60,were randomly divided into low,medium and high dose groups,vehicle control group and positive control group,n = 6. Intragastric administration of rabeprazole sodium were handed 125,250,500 mg·kg - 1 ,and vehicle control group was given sterile distilled water,dosing volume 40 mL·kg - 1;Positive control group was given intraperitoneal injec-tion of cyclophosphamide amide 50 mg·kg - 1 ,dose volume of 20 mL·kg - 1 . After 24 h and 48 h of administration the ani-mals were killed by cervical dislocation,took sternum bone marrow conventional producers,Giemsa staining. Microscopy double - blind read the piece,each mouse was observed 2 000 polychromatic erythrocytes(PCE),micronuclei count ap-peared polychromatic erythrocytes,calculated micronucleus rate,micronucleus rate expressed in parts per thousand,and cal-culated the total proportion of red blood cells and red cells. Results 24 h after oral administration,the bone marrow micro-nucleus incidence of low,medium,high - dose group were 1. 92‰,1. 58‰,1. 83‰,respectively,compared with the vehicle control group(1. 75‰),there had no significant differences. But there were very significant differences(P ﹤ 0. 01)between it and positive control group(23. 92‰). After gavage for 48 h,the incidence of bone marrow of low,medium and high dose group were 1. 75‰,1. 58‰,1. 50‰,respectively,and vehicle control group(1. 83‰)had no significant difference,but had a very significant difference(P ﹤ 0. 01)compared with positive control group(21. 83‰). Conclusion Under the ex-perimental conditions,the result of micronucleus test of the right - handed rabeprazole sodium administration orally in mice was negative.%目的:通过对右旋雷贝拉唑钠小鼠灌胃给药微核试验的研究,预测其遗传毒性,降低临床用药风险。方法健康雄性 BALB/ c 小鼠60只,按体重随机分为低、中、高剂量组、溶媒对照组和阳性对照组,每组6只。分别灌胃给予右旋雷贝拉唑钠125、250、500 mg·kg -1,溶媒对照组灌胃给予灭菌蒸馏水,给药体积40 mL·kg -1;阳性对照组腹腔注射给予环磷酰胺50 mg·kg -1,给药体积为20 mL·kg -1。于给药后24 h 和48 h 将动物颈椎脱臼处死,取胸骨骨髓常规制片、姬姆萨染色。显微镜双盲法阅片,每只小鼠观察2000个嗜多染红细胞(PCE),计数出现微核的嗜多染红细胞,计算微核率,并计算嗜多染红细胞与总红细胞比例。结果研究结果显示,小鼠灌胃给药24 h后,低、中、高剂量组的骨髓微核发生率分别为1.92‰、1.58‰、1.83‰,与溶媒对照组(1.75‰)相比无显著性差异,但其与阳性对照组之间(23.92‰)有非常显著性差异(P ﹤0.01)。在灌胃给药48 h 后,低、中、高剂量组的骨髓微核发生率分别为1.75‰、1.58‰、1.50‰,与溶媒对照组(1.83‰)相比无显著性差异,但其与阳性对照组(21.83‰)之间具有非常显著性差异(P ﹤0.01)。结论在本试验条件下,右旋雷贝拉唑钠小鼠灌胃给药微核试验结果为阴性。