机构地区:[1]中国食品药品检定研究院,国家药物安全评价监测中心,药物非临床安全评价研究北京市重点实验室,北京100176 [2]北京同仁堂股份有限公司科学研究所,北京100079
出 处:《药物不良反应杂志》2024年第9期543-550,共8页Adverse Drug Reactions Journal
摘 要:目的探讨母鼠哺乳期暴露于巴戟天寡糖(MOO)后对Sprague-Dawley(SD)母鼠及其子代大鼠生长发育的影响。方法采用蛇形分组方法,将分娩存活幼仔数≥6只的72只母鼠根据体重分为辅料对照组、MOO低剂量组(50 mg/kg)、中剂量组(160 mg/kg)和高剂量组(500 mg/kg),18只/组。产后0~20 d灌胃给药,每天1次。观察母鼠哺乳期MOO暴露的临床症状以及F1、F2代仔鼠外观、临床症状及大体解剖异常情况,并测量母鼠哺乳期和仔鼠离乳前后的体重和摄食量。采用功能观察组合试验(FOB)对F1、F2代仔鼠的行为学(中枢神经功能)进行评价,采用Y-迷宫实验检测F1代仔鼠的学习记忆功能。将F1代仔鼠饲养至10~12周龄时,进行同剂量组内雌雄动物交配,观察F1代雌鼠的生殖功能。结果哺乳期MOO暴露的各剂量组母鼠临床症状观察均未见异常,母鼠哺乳期体重和日摄食量与辅料对照组相比差异均无统计学意义(均P>0.05)。未发现哺乳期MOO暴露对F1、F2代仔鼠的外观、临床症状、大体解剖、体重和摄食量有明显影响。F1、F2代仔鼠的FOB测试和F1代仔鼠的Y-迷宫测试,仅观察到个别指标在MOO暴露的个别组中存在一定差异,但无明显量效关系。哺乳期各剂量组MOO暴露的F1代雌鼠怀孕后黄体数、着床数、着床率、出生指数、分娩指数、生存指数和离乳指数与辅料对照组相比差异均无统计学意义(均P>0.05)。结论母鼠哺乳期暴露于不同剂量MOO,未见明显毒性反应,其子代动物生长发育、神经系统、学习记忆及生殖功能等均未见异常。Objective To explore the effects of maternal exposure to Morinda officinalis oligosaccharides(MOO)during lactation on the Sprague-Dawley(SD)maternal rats and their offspring's growth and development.Methods Seventy-two female rats with a surviving litter size of≥6 were divided into the excipients control group,MOO low-dose group(50 mg/kg),MOO medium-dose group(160 mg/kg),and MOO high-dose group(500 mg/kg)using a snake-shaped grouping based on body weight,with 18 rats per group.The rats were gavage fed once daily until 20 days of delivery.The response of maternal rats after MOO exposure during lactation,as well as the appearance,response,gross anatomical abnormalities of their F1 and F2 offspring were observed.The body weight and food intake of maternal rats during lactation and those of their offspring before and after weaning were measured.The behavior(central nervous system function)of the F1 and F2 offspring was evaluated using functional observation battery(FOB).The learning and memory function of the F1 offspring was evaluated using Y-maze test.The male and female F1 offspring in the same dose group were mated when they were raised to 10-12 weeks in order to observe the reproductive function of F1 female rats.Results Compared with the excipients control group,no abnormality was found in the clinical observation of maternal rats in the 3 MOO exposure groups during lactation,and there was no significant differences in their body weight and daily food intake during lactation(all P>0.05).No significant effects were found on the appearance,clinical symptoms,gross anatomy,body weight,and food intake of the F1 and F2 offspring after maternal rats receiving MOO exposure during lactation.In the FOB of the F1 and F2 offspring and the Y-maze test of F1 offspring,few differences in MOO exposure groups were observed and lack of significant dose-response relationship.After pregnancy,there were no statistically significant differences in the number of corpus luteum,implantation number,birth index,delivery index,survival
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