乳酸卡德沙星对大鼠围生期生殖毒性研究

Reproduction toxicity of caderofloxacin lactate in perinatal rats

目的研究大鼠围生期和哺乳期给予乳酸卡德沙星对亲代的生殖和胎仔出生后生长发育的影响。方法采用SD大鼠对乳酸卡德沙星进行围生期生殖毒性试验。雌性大鼠妊娠后第15 d至分娩后21 d连续经口灌胃给予乳酸卡德沙星,一日1次。观察并记录孕鼠围生期一般情况、体重、脏器重量及仔鼠的存活率、体重、生理发育情况、神经反射功能、行为活动及生殖能力。结果给药期间,雌鼠(F0代)未见毒性症状。哺乳期,除低剂量(39.5 mg/kg)组与对照组相比差异不明显外,高剂量(158 mg/kg)和中等剂量(79 mg/kg)组雌鼠(F0代)体重均明显降低(P<0.01或P<0.05)。仔鼠(F1代)出生至28 d的平均体重与对照组比较,高剂量组明显偏低(P<0.001或P<0.01或P<0.05);中等剂量组仔鼠(F1代)出生至4 d的平均体重与对照组比较偏低(P<0.001或P<0.05)。各剂量组仔鼠(F1代)各项生理发育指标与对照组相比无显著差异(P>0.05)。高剂量组仔鼠(F1代)断乳前断崖回避反射出现天数显著多于对照组(P<0.01);Y型迷宫试验中,高剂量仔鼠(F1代)的正确进臂次数显著少于对照组(P<0.001)。仔鼠(F1代)生殖功能与对照组比较差异无统计学意义(P>0.05)。结论低剂量(39.5 mg/kg)乳酸卡德沙星对雌鼠生殖和子代生长发育均是安全的。

Objective To evaluate the impact of caderofloxacin lactate on reproductive capability of female rats and growth of fetal rats during the perinatal and lactation period. Methods The female SD rats were orally administered with caderofloxacin lactate once daily from the 15th day of-pregnancy to the 21 th day of parturition. General condition, body weight and organ weight in perinatal period were observed in pregnant rats. Survival rate, body weight, general condition of physiological development, nerve refection, behavior and reproductive capability were observed in fetal rats. Results No toxic symptom was observed in maternal rats （F0） in perinatal period. In lactation period, body weights of maternal rats in high-dose （158 mg/kg） and middle-dose （79 mg/kg） group were significantly lower than those in control group （P〈 0.01, P^0.05）. Meanwhile, there was no significant difference in the body weight of rats between control group and low- dose （39.5 mg/kg） group （P〉0.05）. For the body weight of fetal rats （FI）, significant differences between control group and high-dose group on the 28th day of birth （P〈0：001, P〈0.01, P〈0.05）, and between middle-dose group and control group on the 4th day of birth （P〈0.001, P〈0.05）were observed. There was no significant difference in physiological development among various dose groups and control group （P〉0.05）. However, a significant difference of feted rats in cliff avoidance test between high-dose group and control group （P〈0.01）was observed too. In Y-maze experiment, the number of correct arm entries in high-dose group was significantly lower than that in control group （P〈0.001）. No significant difference was observed in reproduction of fetal rats （F1） from various dose groups and control group. Conclusion Low-dose （39.5 mg/kg） caderofloxacin lactate is safe to reproductive capability of female rats and growth of fetal rats.