高剂量苏氨酸锌和硫酸锌对大鼠胚胎-胎仔发育毒性的比较

Comparison of Teratogenic Effects of Different Zinc Sources at High Dose on Fetuses of Sprague-Dawley(SD) Rats

目的:在胎鼠器官形成期6~15 d对怀孕的Sprague-Dawley(SD)大鼠连续灌胃高剂量锌源,观察苏氨酸锌和硫酸锌对SD大鼠胚胎-胎仔发育毒性。方法:将苏氨酸锌按1 200 mg/(kg·d)的剂量(以体质量计,下同),硫酸锌则给予相同剂量的锌(575 mg/(kg·d)),于妊娠第6~15天连续灌胃给药,观察孕鼠基本生活状况。每隔3 d称1次体质量,妊娠第20天处死孕鼠,记录子宫质量、着床数、死胎数、胎盘质量及胎鼠体质量等,观察活胎仔外观异常与否。每窝1/2胎鼠放入Bouin’s液固定两周作内脏检查,另1/2胎鼠作骨骼畸形检查。结果:苏氨酸锌和硫酸锌组部分孕鼠给药初期均出现食欲低下,毛发不顺等,且摄食量明显降低(P<0.05),实验结束时孕鼠体质量增加显著减少(P<0.05)。苏氨酸锌组有18例胎鼠胸骨缺失,与玉米油组比较有显著差异(P<0.05)。硫酸锌组有13例胎鼠胸骨缺失,同时有2只孕鼠死亡,与玉米油组比较有显著差异(P<0.05)。结论:两种高剂量的锌源对SD孕鼠都有一定的生殖毒性,但苏氨酸锌相对比较安全。

Objective: To observe the toxic effects of zinc threoninate chelate(Thr-Zn) and zinc sulfate on the embryo-fetal development in Sprague-Dawley(SD) rats on days 6 to 15 of pregnancy when they were diluted with corn oil. Methods: The pregnant rats were administered daily with Thr-Zn at a dose of 1 200 mg/(kg·d) bw or the same zinc dose from zinc sulfate(575 mg/(kg·d)) by gavage during days 6 to 15 of pregnancy and the basic living conditions were observed. Body weights were measured on days 0, 4, 8, 12, 16 and 20 of pregnancy, respectively. On day 20, the pregnant rats were sacrificed and their uterus were collected and weighed. The numbers of corpora lutea, implantations, absorbed fetuses, dead fetuses and live fetuses were examined. Fifty percent of fetuses were examined for visceral alterations and the remaining half were examined for skeletal abnormalities. Results: For both the Thr-Zn and zinc sulfate groups on the 7th day, the food intake was significantly decreased(P < 0.05), and the weight gain also was significantly reduced(P < 0.05). The Thr-Zn group had 18 cases of sternal missing and compared with the corn oil group, the difference was statistically significant(P < 0.05). The zinc sulfate group had 13 cases of sternal missing and two pregnant rats died; compared with the corn oil group, the difference was similarly statistically significant(P < 0.05). Conclusions: High-dose administration of the two zinc sources has certain reproductive toxicity on pregnant SD rats, but Thr-Zn is relatively safe.