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目的探讨氟的发育毒性及其作用机理。方法8.5日龄的小鼠胚胎于体外培养系统中给予不同剂量的氟化钠,培养48 h后,观察胚胎生长发育和器官形态分化状况;并应用DTNB直接法测定胚胎组织谷胱甘肽(GSH)水平;以1,6鄄二苯己三烯为荧光探剂,用荧光偏振技术测定卵黄囊细胞膜脂质流动性。结果当培养液中氟浓度为10 mg/L时,卵黄囊直径未发生明显改变,胚胎生长发育和部分器官分化指标明显被抑制;15 mg/L时,畸形胚胎发生率明显升高,主要有前后神经管闭合不全、体翻转不全等(P< 0.05);氟浓度为10 mg/L时,胚胎组织GSH活性和卵黄囊细胞膜脂质流动性也显著降低(P< 0.05)。上述效应均呈现出一定的剂量-效应(反应)关系。结论氟有潜在的致畸性和胚胎毒性,胚胎组织GSH活性和卵黄囊细胞膜脂流动性降低可能在氟致胚胎发育毒性中起重要作用。
Objective To investigate the developmental toxicity of fluorine and its mechanism of action. Methods Mouse embryos at 8 days old were given different doses of sodium fluoride in vitro culture system. After 48 hours of culture, embryonic growth and morphological differentiation were observed. The glutathione (GSH ) Level. Fluorescence polarization was used to determine the lipid fluidity of yolk sac cell membrane by using 1,6-diphenylhexadiene as fluorescent probe. Results When the concentration of fluoride in culture medium was 10 mg / L, the diameter of yolk sac did not change significantly, and the growth and development of embryos and differentiation of some organs were obviously inhibited. At 15 mg / L, the incidence of abnormal embryos was significantly increased (P <0.05). At the concentration of 10 mg / L, the GSH activity in embryonic tissues and the lipid fluidity of the yolk sac cell were also significantly decreased (P <0.05). The above effects show a certain dose-effect (response) relationship. CONCLUSION: Potential teratogenicity and embryotoxicity of fluoride, reduction of GSH activity in embryonic tissue and decrease of fluidity of membrane lipid in yolk sac cells may play an important role in the development of fluoride-induced embryotoxicity.