外源性核苷酸对乙醇致发育毒性的体外干预作用

Intervention Effect of Exogenous Nucleotides on Ethanol-Induced Embryonic Abnormality in Whole Embryo Culture

目的:探讨外源性核苷酸对乙醇致发育毒性的干预作用。方法:采用体外全胚胎培养模型,将胎龄8.5d的ICR小鼠胚胎以4.0g/L乙醇染毒,然后用不同剂量(0.032、0.80、20.0mg/L)的外源性核苷酸干预。培养48h后对小鼠胚胎生长发育和组织器官形态分化进行评分。结果:0.80mg/L核苷酸干预效果最为明显,可使胚胎颅臀长、头长增大,卵黄囊血管分化情况得到改善,并对乙醇所致的体位、心脏、后神经管、后脑、中脑、前脑、听觉、腮弓及前肢芽分化抑制均有改善。0.032mg/L和20.0mg/L剂量组的核苷酸干预也有一定的保护作用,但效果均不及0.80mg/L剂量组。结论:适量补充外源性核苷酸可能对乙醇致发育毒性有拮抗作用。

Objective： to explore the intervention effect of exogenous nucleotides on ethanol-induced embryonic abnormality in whole embryo culture and provide a theoretical reference for future studies. Methods： in vitro post-implantation whole embryo culture was used in this study. Pregnant mice with GD 8.5 were killed by cervical dislocation and the uteri were removed into sterile Hank＇ s solution. The embryos with intact yolk sacs and ectoplacental cones were induced by ethanol, and then subjected to intervention of exogenous nucleotides at the doses of 0.032, 0.80 mg/L and 20.0 mg/L, respectively. The growth and develop- ment of mouse embryos and morphological differentiation of tissues and organs after cultivation for 48 h was evaluated using Maele-Fabry scoring system. Results： an obvious intervention effect was achieved through nucleotide supplementation at the dose of 0.80 mg/L, which could result in an increase of crown-rump length, head length, the differentiation of visceral yolk sac vascular vessels. The scores of flexion, heart, tail neural tube, hindbrain, midbrain, forebrain, otic system, forelimb and branchial arch also revealed a significant increase when compared with ethanol group. Although nucleotide supplementation at the doses of 0.032 mg/L and 20.0 mg/L also exhibited protective effects against ethanol-induced developmental toxicity, the protective effect was weaker when compared with the dose of 0.80 mg/L. Conclusion： nucleotide supplementation at proper dose may be of great benefit for the development of embryos exposed to alcohol in the uterus of mice. Exogenous nucleotides provide an effective strategy for the prevention of ethanol-induced birth defects.