羟基脲对大鼠胚胎中脑细胞增殖和分化的影响

Effects of Hydroxyurea on Cell Proliferation and Differentiation in Rat Embryo Midbrain

背景与目的:为探讨羟基脲(HU)对胚胎发育的作用,采用胚胎中脑细胞微团培养研究HU对细胞增殖和分化的影响。材料与方法:从13d龄的鼠胚胎中分离中脑细胞,加入不同浓度的HU体外连续培养5d,观察细胞分化和细胞增殖情况。结果:对照组原单个分散的细胞形成明显的细胞集落,集落间有丰富的神经纤维,并连结成网状,而不同HU剂量组细胞集落数目减少,集落间的神经纤维束减少,并呈现出剂量-效应关系,显示HU可明显抑制中脑细胞的增殖和分化,阻止神经形成和集落形成过程,HU半数细胞增殖抑制浓度(IcV50)为0.078mmol/L(5.9μg/ml),半数细胞分化抑制浓度(IcD50)为0.018mmol/L(1.37μg/ml),其IcV50与IcD50比值为4.33。结论:HU是一种非特异性细胞增殖和分化抑制剂,具有体外细胞致畸作用。

BACKGROUND ＆AIM： To evaluate the effects of hydroxyurea（HU） on embryonic development, effects of hydroxyurea on proliferation and differentiation were studied by using rat embryo midbrain（central nervous system, CNS） cell micmmass culture. MATERIALS AND METHODS： Midbrain cells from 13-day rat embryos were harvested. After exposed to different doses of hydroxyurea in the culture medium for 5 days, proliferation and differentiation of neurons from midbrain cells were examined. RESULTS： Hydroxyurea could significantly inhibit the proliferation and differentiation of midbrain cells in a dose dependent manner, and could arrest neurogenesis and colony formation. The numbers of differentiated foci decreased with increasing concentration of HU, and nerve fiber bundle reduced during the differentiated foci, showing a typical dose-effect relationship. The IcV50 value of hydroxyurea was 0.078 mmol/L（5.9 μg/ml） and the IcD50 value was 0.018 mmol/L（1.37 μg/ml）. The ratio of IcV50 and IcD50 was 4.33. CONCLUSION： Hydroxyurea is a non-specific inhibitor of cell proliferation and differentiation; it could potentially result in teratogenicity in vitro.