甲硝唑对受孕小鼠的致畸作用

Teratogenicity of metronidazole in pregnant mouse

目的研究不同剂量甲硝唑对受孕小鼠的致畸作用。方法按照体重将检出的孕鼠随机分为4组:3个剂量实验组和对照组,每组25只。对照组(不服药),低、中、高3个剂量实验组服用甲硝唑1.25,2.50,5.00 mg·kg^(-1),在受孕7~15 d给药。计算死胎率和吸收胎率。检查外观、骨骼、心脏的致畸情况。结果对照组和低、中、高3个剂量实验组的活胎率分别为96%和93%,83%,60%;这4组的吸收胎率分别为3.8%和7.1%,17%,40%,中、高2个剂量实验组与对照组比较,差异均有统计学意义(均P<0.001)。与对照组的外部畸形率为0比较,中、高2个剂量实验组分别为1.5%,6.8%,差异均有统计学意义(P<0.05,P<0.001)。对照组的骨骼致畸率和心脏致畸率分别为0.8%,0,高剂量实验组分别为8.9%,4.1%,差异均有统计学意义(均P<0.001)。结论甲硝唑服用剂量较大时,对受孕小鼠的致畸作用较大,发生骨骼畸形的概率较大。

Objective To study the teratogenic effects of metronidazole on pregnant mice. Methods The pregnant mouse was divided into four groups, each group had 25 mouse： control group without drugs; low, middle and high doses experimental groups were oral 1.25,2. 50,5.00 mg ·kg-1 metronidazole at 7 - 15 d after fertilization. The rate of still-birth and absorption rate were calculated. The teratogenicity of the appearance, bone and heart were examined. Results The rate of stillbirth in control group and low, middle and high doses experimental groups were 96% and 93%, 83%, 60%. The absorption rate in four groups were 3. 8% and 7.1%, 17% ,40%, compared with control group and middle, high doses experimental groups, the differnce was significant （P 〈0. 001 ）. Compared with control group on exterior deformity rate （0）, it were 1.5%, 6.8% in middle and high doses experimental groups, the difference was significantly（P 〈0. 05 ,P 〈0. 001 ）. Compared with control group on skeletal deformity rate and heart deformity rate （0. 8% ,0） ,it were 8.9% ,4. 1% in high doses experimental group, the difference was significant （ all P 〈 0. 001 ） . Conclusion Teratogenic effects is larger when metronidazole dose is greater, the probability of occurrence of skeletal malformations.