不同剂量锌缺乏对小鼠及其胚胎发育的影响

EFFECT OF DIFFERENT LEVELS OF ZINC DEFICIENCY ON THE DEVELOPMENT OF FEMALE MICE AND THEIR FETUS

目的 : 用昆明种雌性小鼠建立成不同程度缺锌动物模型 ,研究不同程度锌缺乏和孕早期补锌对小鼠及其胚胎发育的影响 ,并探求其发育毒性作用的阈剂量。方法 : 实验分两阶段进行。实验一用 36只初断乳 1 4～ 1 8g小鼠 ,分为低锌 (ZD)、中锌 (ZM)、常锌 (ZN)三组 ,喂饲含锌分别为 3.0± 0 .5、1 5、30 mg/kg的饲料 ,经 50 d喂养平均体重达 30 g后交配。实验二选用 80只 ,2 5～ 30 g成熟小鼠 ,随机分为低锌组 [ZD,饲料含锌 (3.0± 0 .5) mg/kg];低锌补锌组 (ZS,于孕第 7d将低锌饲料换为含锌 30 mg/kg的常锌饲料 ) ;边缘缺锌组 (MD,饲料含锌 9mg/kg) ;常锌组(ZN,饲料含锌 30 mg/kg)。 2 5d锌耗竭性喂养后交配。所有孕鼠于妊第 1 8d活杀。结果 : 实验一 :低锌组小鼠锌水平显著低于常锌组 (P<0 .0 5) ,有典型缺锌症状 ,几乎全部出现生长抑制 ,58.33%的小鼠衰竭死亡 ,存活小鼠亦不能正常交配妊娠。 1 5mg/kg剂量组小鼠则生长发育良好 ,各项指标与常锌组间无异 (P>0 .0 5)。实验二 :ZD组小鼠血清碱性磷酸酶 (AKP)活性 ,股骨锌含量显著低于 ZN组 (P<0 .0 1 ) ;该组小鼠胚胎有明显发育不良 ,畸胎及死胎出现率显著高于 ZN组 (P<0 .0 1 )。ZS组小鼠在孕第 7d补锌后活胎仔大小已趋正常 (P>0 .0 5) ,畸胎出现率与 ZD?

Objective: To determine the effects of different levels of zinc deficiency and zinc supplementation in the early stage of pregnancy on the development of the female mice and their fetus, and the lowest toxic level was also investigated. [WT5FZ]Methods: The model of zinc deficiency (ZD) was established on Kunmin mice and the experiment included two parts. Part one: 36 female mice (14～18 g) were randomly divided into 3 groups, zinc deficient group (ZD); middle zinc group (ZM); normal zinc group (ZN). They were fed for 50 days and mated with male mice. Part two: 80 female mice (25～30 g) were randomly divided into 4 groups, zinc deficient group (ZD); zinc suppplemented group (ZS); zinc marginally deficient group (MD); normal zinc group (ZN). They were fed 25 days for depleting the zinc store in body, then mated with male mice. All the pregnant mice were killed on the 18 th day of pregnancy. The content of zinc in diet for different levels groups were: (3.0±0.5) mg/kg (ZD), 9 mg/kg (MD group), 15 mg/kg (ZM), 30 mg/kg (ZN).The mice in group ZS were fed ZD diet at first and then were changed to ZN diet at the 7 th day of pregnancy. [WT5FZ]Results: Part one: 1. The zinc content in serum was lower in ZD group (P<0.05). 2. The growth of the ZD group mice was seriously retarded and most of them could not mature and reproduce normaly, even died for poor nutrition. Part two: 1. As compared with ZN group, the serum AKP activity and femur zinc content in ZD group were significantly lower (P<0.01), and they were lower in group ZS, MD too. (P<0.05). 2. Pregnancy did not show differences among groups, but the mice with malformed and dead fetus were seriously higher in group ZD and ZS than group ZN (P<0.05). The fetus with smaller size, malformation and early dead ones were also higher in group ZD than in group ZN. 3. The fetus in group ZS were normal in size and the teratogenicity was lower compared with group ZD (P<0.01), but the dead embryo rate was still higher than group ZN (P<0.05). [WT5FZ]Conclusion: 1. Serious zinc deficiency [(3.0±0.5) mg/kg] can inhibit the growth of immature mouse and prevent its maturity and reproduction, and its teratogenicity and embryo lethality were notable. 2. Marginal zinc deficient diet (9 mg/kg) do not affect the fetus size, but their dead and malformed fetus rates were different from group ZD and ZN. 3. By supplementing zinc in the early stage of pregnancy, the malformed fetus rate decrease, but its embryo lethality is still existing. 4. 15 mg/kg zinc content in diet does not show any harmful effect.